Bisphenol A and its Alternatives in Food Packaging



3724275-34290000left-901636003181350140970Work PlanImplementation: 4000020000Work PlanImplementation: Bisphenol A and its Alternatives in Food PackagingOctober 2019Prepared by right186245500IntroductionThe Safer Consumer Products regulations define the process and criteria used by the Department of Toxic Substances Control (DTSC) to evaluate consumer products for possible designation as Priority Products. In that process, DTSC issues a Priority Product Work Plan (Work Plan) identifying the product categories to evaluate over a three-year period. DTSC then considers the product categories through the lens of the Work Plan’s stated policy goals (Figure 1). Since issuing the 2018-2020 Work Plan, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"l9jMEfbk","properties":{"formattedCitation":"\\super 1\\nosupersub{}","plainCitation":"1","noteIndex":0},"citationItems":[{"id":3719,"uris":[""],"uri":[""],"itemData":{"id":3719,"type":"webpage","title":"2018-2020 Priority Product Work Plan","URL":"","language":"en","author":[{"family":"DTSC","given":"(Department of Toxic Substances Control)"}],"accessed":{"date-parts":[["2019",8,7]]}}}],"schema":""} 1 DTSC has conducted a review of product categories, chemicals, and chemical classes that align with our policy goals. This document summarizes our preliminary findings on food packaging containing bisphenol A (BPA) and its alternatives, and describes our concerns. Publication of this document signals the beginning of a dialogue with interested stakeholders, including manufacturers, nonprofit organizations, governments, and academia, to inform DTSC on the potential listing of specific consumer products containing BPA and its alternatives as one or more Priority Products subject to the requirements of the Safer Consumer Products regulations. Figure SEQ Figure \* ARABIC 1. An overview of the Safer Consumer Products regulations.BackgroundDTSC’s 2018-2020 Priority Product Work Plan ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"CuwrGpc4","properties":{"formattedCitation":"\\super 1\\nosupersub{}","plainCitation":"1","noteIndex":0},"citationItems":[{"id":3719,"uris":[""],"uri":[""],"itemData":{"id":3719,"type":"webpage","title":"2018-2020 Priority Product Work Plan","URL":"","language":"en","author":[{"family":"DTSC","given":"(Department of Toxic Substances Control)"}],"accessed":{"date-parts":[["2019",8,7]]}}}],"schema":""} 1 adopted policy goals to guide DTSC in prioritizing Priority Products. In considering the product categories in the Work Plan and our policy goals, DTSC identified BPA, as well as some of its analogues and alternatives, as Candidate Chemicals that may warrant further research regarding their use in food packaging products. This research would address two of the policy goals outlined in the Work Plan:to protect children from exposure to harmful chemicals, especially carcinogens, mutagens, reproductive toxicants, neurotoxicants, developmental toxicants, and endocrine disruptors; andto protect Californians from chemicals that migrate into food from food packaging.BPA is one of the most studied environmental contaminants in the world and has been classified as an endocrine disrupting chemical due to its ability to disrupt estrogen, androgen, and thyroid-hormone mediated biological pathways. One of the major uses of BPA is to manufacture epoxy-based resins that coat the interior of aluminum and steel food and beverage cans. BPA may also be used in other food packaging liners, such as jar lids and bottle caps (collectively referred to as “lids” within this document). Liners protect the metal packaging from corrosion, act as inert barriers to a wide variety of food types, and are sufficiently flexible and adhesive for use during can/lid manufacturing processes. It has been well documented that, under certain conditions, BPA is capable of migrating out of these liners and into food items, leading to the potential for subsequent dietary exposure in humans.Public awareness concerning the risks associated with BPA exposure has created market pressure to remove it from food packaging applications. Many food packaging manufacturers have proactively removed BPA from their products, even though the U.S. Food and Drug Administration considers its use in food packaging materials as safe. However, other bisphenols, such as bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF), which are all on DTSC’s Candidate Chemical List, may be used as drop-in replacements for BPA, and many of these compounds exhibit similar endocrine disrupting properties as BPA. Non-bisphenol chemicals may also be used to manufacture can and lid liners, such as glycidyl methacrylate, a possible BPA replacement. Glycidyl methacrylate has been classified as a Category 1B carcinogen and reproductive toxicant by the European Chemicals Agency (ECHA), and is also on DTSC’s Candidate Chemical List. At this time, the prevalence and application of BPA and its chemical alternatives that manufacturers may be using in liners for food and beverage cans and lids are unknown to DTSC. DTSC is requesting additional information from stakeholders about the specific use of bisphenols in food packaging products, the adverse impacts associated with the life cycle of these products, and the availability and feasibility of alternatives. Please see the Questions to Stakeholders section below.Preliminary Screening ResultsHazard TraitsThe hazard traits of BPA are well defined in the scientific literature and include developmental toxicity, reproductive toxicity, endocrine toxicity, immunotoxicity, and neurodevelopmental toxicity. BPA has been robustly studied in animal models, in vitro models, and in human epidemiological cohorts ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"xxgLIVWl","properties":{"formattedCitation":"\\super 2,3\\nosupersub{}","plainCitation":"2,3","noteIndex":0},"citationItems":[{"id":2747,"uris":[""],"uri":[""],"itemData":{"id":2747,"type":"article-journal","title":"Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects","container-title":"The Journal of Steroid Biochemistry and Molecular Biology","collection-title":"Endocrine Disruptors","page":"27-34","volume":"127","issue":"1","source":"ScienceDirect","abstract":"Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. This compound is a building block of polycarbonate plastics often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and beverage containers. Studies have shown that BPA can leach from these and other products in contact with food and drink, and as a result, routine ingestion of BPA is presumed. This compound is also found in an enormous number of other products that we come into contact with daily, and therefore it is not surprising that it has been detected in the majority of individuals examined. BPA is a known endocrine disruptor. Although initially considered to be a weak environmental estrogen, more recent studies have demonstrated that BPA may be similar in potency to estradiol in stimulating some cellular responses. Moreover, emerging evidence suggests that BPA may influence multiple endocrine-related pathways. Studies in rodents have identified adverse effects of BPA at levels at or below the current acceptable daily intake level for this compound. The various reported adverse effects of BPA are reviewed, and potential mechanisms of BPA action are discussed. Much more investigation is needed to understand the potential adverse health effects of BPA exposure in humans and to understand the multiple pathways through which it may act. Although many questions remain to be answered, it is becoming increasingly apparent that exposure to BPA is ubiquitous and that the effects of this endocrine disruptor are complex and wide-ranging.","DOI":"10.1016/j.jsbmb.2011.05.002","ISSN":"0960-0760","shortTitle":"Bisphenol A","journalAbbreviation":"The Journal of Steroid Biochemistry and Molecular Biology","author":[{"family":"Rubin","given":"Beverly S."}],"issued":{"date-parts":[["2011",10,1]]}}},{"id":2312,"uris":[""],"uri":[""],"itemData":{"id":2312,"type":"article-journal","title":"Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis","container-title":"Environment International","page":"343-356","volume":"114","source":"PubMed","abstract":"BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans.\nOBJECTIVES: Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD.\nDATA SOURCES: Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017.\nSTUDY ELIGIBILITY CRITERIA: For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at <3?months of age for humans, up to postnatal day 35 for rats and up to postnatal day 40 for mice. Exposure could occur either gestationally (via maternal exposure) or directly to the offspring.\nSTUDY APPRAISAL AND SYNTHESIS METHODS: Studies were evaluated using the OHAT risk of bias tool. The effects in humans were assessed qualitatively. For rodents exposed to 20?μg/kg/day BPA, we evaluated the study findings in a random effects meta-analytical model.\nRESULTS: A review of the literature identified 29 rodent and 3 human studies. A random effects meta-analysis showed significantly increased hyperactivity in male rodents. In humans, early BPA exposure was associated with hyperactivity in boys and girls.\nLIMITATIONS, CONCLUSIONS, AND IMPLICATIONS OF KEY FINDINGS: We concluded that early life BPA exposure is a presumed human hazard for the development of hyperactivity. Possible limitations of this systematic review include deficiencies in author reporting, exclusion of some literature based on language, and insufficient similarity between human studies. SRs that result in hazard-based conclusions are the first step in assessing and mitigating risks. Given the widespread exposure of BPA and increasing diagnoses of ADHD, we recommend immediate actions to complete such risk analyses and take next steps for the protection of human health. In the meantime, precautionary measures should be taken to reduce exposure in pregnant women, infants and children. The present analysis also discusses potential mechanisms by which BPA affects hyperactivity, and the most effective avenues for future research.\nSYSTEMATIC REVIEW REGISTRATION NUMBER: Not available.","DOI":"10.1016/j.envint.2017.12.028","ISSN":"1873-6750","note":"PMID: 29525285","shortTitle":"Prenatal exposure to bisphenol A and hyperactivity in children","journalAbbreviation":"Environ Int","language":"eng","author":[{"family":"Rochester","given":"Johanna R."},{"family":"Bolden","given":"Ashley L."},{"family":"Kwiatkowski","given":"Carol F."}],"issued":{"date-parts":[["2018"]]}}}],"schema":""} 2,3. Many associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes have been shown. For example, many published scientific studies have shown BPA to be associated with changes in neuronal development ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"IWXuKM5w","properties":{"formattedCitation":"\\super 4\\uc0\\u8211{}7\\nosupersub{}","plainCitation":"4–7","noteIndex":0},"citationItems":[{"id":2666,"uris":[""],"uri":[""],"itemData":{"id":2666,"type":"article-journal","title":"Prenatal bisphenol a exposure and child behavior in an inner-city cohort","container-title":"Environmental Health Perspectives","page":"1190-1194","volume":"120","issue":"8","source":"PubMed","abstract":"BACKGROUND: Experimental laboratory evidence suggests that bisphenol A (BPA), an endocrine disruptor, is a neurodevelopmental toxicant. However, there have been limited and inconclusive results with respect to sex-specific BPA effects on child behavior.\nOBJECTIVE: We examined the association between prenatal BPA exposure and child behavior, adjusting for postnatal BPA exposure and hypothesizing sex-specific effects.\nMETHODS: We followed African-American and Dominican women and their children from pregnancy to child's age 5 years, collecting spot urine samples from the mothers during pregnancy (34 weeks on average) and from children between 3 and 4 years of age to estimate BPA exposure. We assessed child behavior between 3 and 5 years of age using the Child Behavior Checklist (CBCL) and used generalized linear models to test the association between BPA exposure and child behavior, adjusting for potential confounders.\nRESULTS: The analysis was conducted on 198 children (87 boys and 111 girls). Among boys, high prenatal BPA exposure (highest quartile vs. the lowest three quartiles) was associated with significantly higher CBCL scores (more problems) on Emotionally Reactive [1.62 times greater; 95% confidence interval (CI): 1.13, 2.32] and Aggressive Behavior syndromes (1.29 times greater; 95% CI: 1.09, 1.53). Among girls, higher exposure was associated with lower scores on all syndromes, reaching statistical significance for Anxious/Depressed (0.75 times as high; 95% CI: 0.57, 0.99) and Aggressive Behavior (0.82 times as high; 95% CI: 0.70, 0.97).\nCONCLUSION: These results suggest that prenatal exposure to BPA may affect child behavior, and differently among boys and girls.","DOI":"10.1289/ehp.1104492","ISSN":"1552-9924","note":"PMID: 22543054\nPMCID: PMC3440080","journalAbbreviation":"Environ. Health Perspect.","language":"eng","author":[{"family":"Perera","given":"Frederica"},{"family":"Vishnevetsky","given":"Julia"},{"family":"Herbstman","given":"Julie B."},{"family":"Calafat","given":"Antonia M."},{"family":"Xiong","given":"Wei"},{"family":"Rauh","given":"Virginia"},{"family":"Wang","given":"Shuang"}],"issued":{"date-parts":[["2012",8]]}}},{"id":2668,"uris":[""],"uri":[""],"itemData":{"id":2668,"type":"article-journal","title":"Bisphenol A in relation to behavior and learning of school-age children","container-title":"Journal of Child Psychology and Psychiatry, and Allied Disciplines","page":"890-899","volume":"54","issue":"8","source":"PubMed","abstract":"BACKGROUND: Bisphenol A (BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior.\nMETHODS: Urinary BPA concentrations and behavioral and learning characteristics were assessed in a general population of 1,089 children, aged 8-11 years. The main outcome measures were the Child Behavior Checklist (CBCL) and the Learning Disability Evaluation Scale (LDES).\nRESULTS: Urinary levels of BPA were positively associated with the CBCL total problems score and negatively associated with the learning quotient from the LDES. The linear association with the CBCL anxiety/depression score and the quadratic association with the LDES listening score were significant after correction for multiple comparisons.\nCONCLUSIONS: Environmental exposure to BPA might be associated with childhood behavioral and learning development. The results suggest possible nonmonotonic relationships.","DOI":"10.1111/jcpp.12050","ISSN":"1469-7610","note":"PMID: 23445117","journalAbbreviation":"J Child Psychol Psychiatry","language":"eng","author":[{"family":"Hong","given":"Soon-Beom"},{"family":"Hong","given":"Yun-Chul"},{"family":"Kim","given":"Jae-Won"},{"family":"Park","given":"Eun-Jin"},{"family":"Shin","given":"Min-Sup"},{"family":"Kim","given":"Boong-Nyun"},{"family":"Yoo","given":"Hee-Jeong"},{"family":"Cho","given":"In-Hee"},{"family":"Bhang","given":"Soo-Young"},{"family":"Cho","given":"Soo-Churl"}],"issued":{"date-parts":[["2013",8]]}}},{"id":2767,"uris":[""],"uri":[""],"itemData":{"id":2767,"type":"article-journal","title":"Impact of Early-Life Bisphenol A Exposure on Behavior and Executive Function in Children","container-title":"PEDIATRICS","page":"873-882","volume":"128","issue":"5","source":"Crossref","abstract":"OBJECTIVES: To estimate the impact of gestational and childhood bisphenol A (BPA) exposures on behavior and executive function at 3 years of age and to determine whether child gender modi?ed those associations.\nMETHODS: We used a prospective birth cohort of 244 mothers and their 3-year-old children from the greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of gestation and birth) and child (1, 2, and 3 years of age) urine samples, respectively. Behavior and executive function were measured by using the Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P).\nRESULTS: BPA was detected in ?97% of the gestational (median: 2.0 ?g/L) and childhood (median: 4.1 ?g/L) urine samples. With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on the BASC-2 and poorer emotional control and inhibition on the BRIEF-P. The magnitude of the gestational BPA associations differed according to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among girls, but changes were null or negative among boys. Associations between childhood BPA exposure and neurobehavior were largely null and not modi?ed by child gender.\nCONCLUSIONS: In this study, gestational BPA exposure affected behavioral and emotional regulation domains at 3 years of age, especially among girls. Clinicians may advise concerned patients to reduce their exposure to certain consumer products, but the bene?ts of such reductions are unclear. Pediatrics 2011;128:873–882","DOI":"10.1542/peds.2011-1335","ISSN":"0031-4005, 1098-4275","language":"en","author":[{"family":"Braun","given":"J. M."},{"family":"Kalkbrenner","given":"A. E."},{"family":"Calafat","given":"A. M."},{"family":"Yolton","given":"K."},{"family":"Ye","given":"X."},{"family":"Dietrich","given":"K. N."},{"family":"Lanphear","given":"B. P."}],"issued":{"date-parts":[["2011",11,1]]}}},{"id":2771,"uris":[""],"uri":[""],"itemData":{"id":2771,"type":"article-journal","title":"Bisphenol A exposure and children’s behavior: A systematic review","container-title":"Journal of Exposure Science & Environmental Epidemiology","page":"175-183","volume":"27","issue":"2","source":"Crossref","DOI":"10.1038/jes.2016.8","ISSN":"1559-0631, 1559-064X","shortTitle":"Bisphenol A exposure and children’s behavior","language":"en","author":[{"family":"Ejaredar","given":"Maede"},{"family":"Lee","given":"Yoonshin"},{"family":"Roberts","given":"Derek J"},{"family":"Sauve","given":"Reginald"},{"family":"Dewey","given":"Deborah"}],"issued":{"date-parts":[["2017",3]]}}}],"schema":""} 4–7, decreased fertility ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"rpHFsvjk","properties":{"formattedCitation":"\\super 8\\nosupersub{}","plainCitation":"8","noteIndex":0},"citationItems":[{"id":2724,"uris":[""],"uri":[""],"itemData":{"id":2724,"type":"article-journal","title":"Evidence for bisphenol A-induced female infertility: a review (2007-2016)","container-title":"Fertility and Sterility","page":"827-856","volume":"106","issue":"4","source":"PubMed","abstract":"We summarized the scientific literature published from 2007 to 2016 on the potential effects of bisphenol A (BPA) on female fertility. We focused on overall fertility outcomes (e.g., ability to become pregnant, number of offspring), organs that are important for female reproduction (i.e., oviduct, uterus, ovary, hypothalamus, and pituitary), and reproductive-related processes (i.e., estrous cyclicity, implantation, and hormonal secretion). The reviewed literature indicates that BPA may be associated with infertility in women. Potential explanations for this association can be generated from experimental studies. Specifically, BPA may alter overall female reproductive capacity by affecting the morphology and function of the oviduct, uterus, ovary, and hypothalamus-pituitary-ovarian axis in animal models. In addition, BPA may disrupt estrous cyclicity and implantation. Nevertheless, further studies are needed to better understand the exact mechanisms of action and to detect potential reproductive toxicity at earlier stages.","DOI":"10.1016/j.fertnstert.2016.06.027","ISSN":"1556-5653","note":"PMID: 27417731\nPMCID: PMC5026908","shortTitle":"Evidence for bisphenol A-induced female infertility","journalAbbreviation":"Fertil. Steril.","language":"eng","author":[{"family":"Ziv-Gal","given":"Ayelet"},{"family":"Flaws","given":"Jodi A."}],"issued":{"date-parts":[["2016"]],"season":"15"}}}],"schema":""} 8, endocrine changes ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"QP1iFlsj","properties":{"formattedCitation":"\\super 9\\uc0\\u8211{}11\\nosupersub{}","plainCitation":"9–11","noteIndex":0},"citationItems":[{"id":2683,"uris":[""],"uri":[""],"itemData":{"id":2683,"type":"article-journal","title":"In vitro molecular mechanisms of bisphenol A action","container-title":"Reproductive Toxicology (Elmsford, N.Y.)","page":"178-198","volume":"24","issue":"2","source":"PubMed","abstract":"Bisphenol A (BPA, 2,2-bis (4-hydroxyphenyl) propane; CAS# 80-05-7) is a chemical used primarily in the manufacture of polycarbonate plastic, epoxy resins and as a non-polymer additive to other plastics. Recent evidence has demonstrated that human and wildlife populations are exposed to levels of BPA which cause adverse reproductive and developmental effects in a number of different wildlife species and laboratory animal models. However, there are major uncertainties surrounding the spectrum of BPA's mechanisms of action, the tissue-specific impacts of exposures, and the critical windows of susceptibility during which target tissues are sensitive to BPA exposures. As a foundation to address some of those uncertainties, this review was prepared by the \"In vitro\" expert sub-panel assembled during the \"Bisphenol A: An Examination of the Relevance of Ecological, In vitro and Laboratory Animal Studies for Assessing Risks to Human Health\" workshop held in Chapel Hill, NC, Nov 28-29, 2006. The specific charge of this expert panel was to review and assess the strength of the published literature pertaining to the mechanisms of BPA action. The resulting document is a detailed review of published studies that have focused on the mechanistic basis of BPA action in diverse experimental models and an assessment of the strength of the evidence regarding the published BPA research.","DOI":"10.1016/j.reprotox.2007.05.010","ISSN":"0890-6238","note":"PMID: 17628395","journalAbbreviation":"Reprod. Toxicol.","language":"eng","author":[{"family":"Wetherill","given":"Yelena B."},{"family":"Akingbemi","given":"Benson T."},{"family":"Kanno","given":"Jun"},{"family":"McLachlan","given":"John A."},{"family":"Nadal","given":"Angel"},{"family":"Sonnenschein","given":"Carlos"},{"family":"Watson","given":"Cheryl S."},{"family":"Zoeller","given":"R. Thomas"},{"family":"Belcher","given":"Scott M."}],"issued":{"date-parts":[["2007",9]]}}},{"id":2685,"uris":[""],"uri":[""],"itemData":{"id":2685,"type":"article-journal","title":"Bisphenol A affects androgen receptor function via multiple mechanisms","container-title":"Chemico-Biological Interactions","page":"556-564","volume":"203","issue":"3","source":"PubMed","abstract":"Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.","DOI":"10.1016/j.cbi.2013.03.013","ISSN":"1872-7786","note":"PMID: 23562765\nPMCID: PMC3722857","journalAbbreviation":"Chem. Biol. Interact.","language":"eng","author":[{"family":"Teng","given":"Christina"},{"family":"Goodwin","given":"Bonnie"},{"family":"Shockley","given":"Keith"},{"family":"Xia","given":"Menghang"},{"family":"Huang","given":"Ruili"},{"family":"Norris","given":"John"},{"family":"Merrick","given":"B. Alex"},{"family":"Jetten","given":"Anton M."},{"family":"Austin","given":"Christopher P."},{"family":"Tice","given":"Raymond R."}],"issued":{"date-parts":[["2013",5,25]]}}},{"id":2689,"uris":[""],"uri":[""],"itemData":{"id":2689,"type":"article-journal","title":"A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA)","container-title":"Hormones and Behavior","page":"59-67","volume":"101","source":"PubMed","abstract":"Bisphenol-A (BPA) is a well-known endocrine disrupting compound (EDC), capable of affecting the normal function and development of the reproductive system, brain, adipose tissue, and more. In spite of these diverse and well characterized effects, there is often comparatively little known about the molecular mechanisms which bring them about. BPA has traditionally been regarded as a primarily estrogenic EDC, and this perspective is often what guides research into the effects of BPA. However, emerging data from in-vitro and in-silico models show that BPA binds with a significant number of hormone receptors, including a number of nuclear and membrane-bound estrogen receptors, androgen receptors, as well as the thyroid hormone receptor, glucocorticoid receptor, and PPARγ. With this increased diversity of receptor targets, it may be possible to explain some of the more puzzling aspects of BPA pharmacology, including its non-monotonic dose-response curve, as well as experimental results which disagree with estrogenic positive controls. This paper reviews the receptors for which BPA has a known interaction, and discusses the implications of taking these receptors into account when studying the disruptive effects of BPA on growth and development.","DOI":"10.1016/j.yhbeh.2017.11.001","ISSN":"1095-6867","note":"PMID: 29104009","shortTitle":"A plurality of molecular targets","journalAbbreviation":"Horm Behav","language":"eng","author":[{"family":"MacKay","given":"Harry"},{"family":"Abizaid","given":"Alfonso"}],"issued":{"date-parts":[["2018",5]]}}}],"schema":""} 9–11, and metabolic ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1kANFYYi","properties":{"formattedCitation":"\\super 12,13\\nosupersub{}","plainCitation":"12,13","noteIndex":0},"citationItems":[{"id":2702,"uris":[""],"uri":[""],"itemData":{"id":2702,"type":"article-journal","title":"Bisphenol-A and metabolic diseases: epigenetic, developmental and transgenerational basis","container-title":"Environmental Epigenetics","page":"dvw022","volume":"2","issue":"3","source":"PubMed","abstract":"Exposure to environmental toxicants is now accepted as a factor contributing to the increasing incidence of obesity and metabolic diseases around the world. Such environmental compounds are known as 'obesogens'. Among them, bisphenol-A (BPA) is the most widespread and ubiquitous compound affecting humans and animals. Laboratory animal work has provided conclusive evidence that early-life exposure to BPA is particularly effective in predisposing individuals to weight gain. Embryonic exposure to BPA is reported to generate metabolic disturbances later in life, such as obesity and diabetes. When BPA administration is combined with a high-fat diet, there is an exacerbation in the development of metabolic disorders. Remarkably, upon BPA exposure of gestating females, metabolic disturbances have been found both in the offspring and later in life in the mothers themselves. When considering the metabolic effects generated by an early developmental exposure to BPA, one of the questions that arises is the role of precursor cells in the etiology of metabolic disorders. Current evidence shows that BPA and other endocrine disruptors have the ability to alter fat tissue development and growth by affecting the capacity to generate functional adipocytes, as well as their rate of differentiation to specific cell types. Epigenetic mechanisms seem to be involved in the BPA-induced effects related to obesity, as they have been described in both in vitro and in vivo models. Moreover, recent reports also show that developmental exposure to BPA generates abnormalities that can be transmitted to future generations, in a process called as transgenerational epigenetic inheritance.","DOI":"10.1093/eep/dvw022","ISSN":"2058-5888","note":"PMID: 29492299\nPMCID: PMC5804535","shortTitle":"Bisphenol-A and metabolic diseases","journalAbbreviation":"Environ Epigenet","language":"eng","author":[{"family":"Alonso-Magdalena","given":"Paloma"},{"family":"Rivera","given":"Francisco J."},{"family":"Guerrero-Bosagna","given":"Carlos"}],"issued":{"date-parts":[["2016",8]]}}},{"id":2762,"uris":[""],"uri":[""],"itemData":{"id":2762,"type":"article-journal","title":"Bisphenol A at Environmentally Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes","container-title":"Environmental Health Perspectives","page":"1642-1647","volume":"116","issue":"12","source":"Crossref","abstract":"BACKGROUND: The incidence of obesity has risen dramatically over the last few decades. This epidemic may be affected by exposure to xenobiotic chemicals. Bisphenol A (BPA), an endocrine disruptor, is detectable at nanomolar levels in human serum worldwide. Adiponectin is an adipocyte-speci?c hormone that increases insulin sensitivity and reduces tissue in?ammation. Thus, any factor that suppresses adiponectin release could lead to insulin resistance and increased susceptibility to obesity-associated diseases.\nOBJECTIVES: In this study we aimed to compare a) the effects of low doses of BPA and estradiol (E2) on adiponectin secretion from human breast, subcutaneous, and visceral adipose explants and mature adipocytes, and b) expression of putative estrogen and estrogen-related receptors (ERRs) in these tissues.\nMETHODS: We determined adiponectin levels in conditioned media from adipose explants or adipocytes by enzyme-linked immunosorbant assay. We determined expression of estrogen receptors (ERs) α and β, G-protein–coupled receptor 30 (GPR30), and ERRs α, β, and γ by quantitative realtime polymerase chain reaction.\nRESULTS: BPA at 0.1 and 1 nM doses suppressed adiponectin release from all adipose depots examined. Despite substantial variability among patients, BPA was as effective, and often more effective, than equimolar concentrations of E2. Adipose tissue expresses similar mRNA levels of ERα, ERβ, and ERRγ, and 20- to 30-fold lower levels of GPR30, ERRα, and ERRβ.\nCONCLUSIONS: BPA at environmentally relevant doses inhibits the release of a key adipokine that protects humans from metabolic syndrome. The mechanism by which BPA suppresses adiponectin and the receptors involved remains to be determined.","DOI":"10.1289/ehp.11537","ISSN":"0091-6765, 1552-9924","language":"en","author":[{"family":"Hugo","given":"Eric R."},{"family":"Brandebourg","given":"Terry D."},{"family":"Woo","given":"Jessica G."},{"family":"Loftus","given":"Jean"},{"family":"Alexander","given":"J. Wesley"},{"family":"Ben-Jonathan","given":"Nira"}],"issued":{"date-parts":[["2008",12]]}}}],"schema":""} 12,13, cardiovascular ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"HUfLKpAo","properties":{"formattedCitation":"\\super 14\\nosupersub{}","plainCitation":"14","noteIndex":0},"citationItems":[{"id":2700,"uris":[""],"uri":[""],"itemData":{"id":2700,"type":"article-journal","title":"Impact of bisphenol a on the cardiovascular system - epidemiological and experimental evidence and molecular mechanisms","container-title":"International Journal of Environmental Research and Public Health","page":"8399-8413","volume":"11","issue":"8","source":"PubMed","abstract":"Bisphenol A (BPA) is a ubiquitous plasticizing agent used in the manufacturing of polycarbonate plastics and epoxy resins. There is well-documented and broad human exposure to BPA. The potential risk that BPA poses to the human health has attracted much attention from regulatory agencies and the general public, and has been extensively studied. An emerging and rapidly growing area in the study of BPA's toxicity is its impact on the cardiovascular (CV) system. Recent epidemiological studies have shown that higher urinary BPA concentration in humans is associated with various types of CV diseases, including angina, hypertension, heart attack and coronary and peripheral arterial disease. Experimental studies have demonstrated that acute BPA exposure promotes the development of arrhythmias in female rodent hearts. Chronic exposure to BPA has been shown to result in cardiac remodeling, atherosclerosis, and altered blood pressure in rodents. The underlying mechanisms may involve alteration of cardiac Ca2+ handling, ion channel inhibition/activation, oxidative stress, and genome/transcriptome modifications. In this review, we discuss these recent findings that point to the potential CV toxicity of BPA, and highlight the knowledge gaps in this growing research area.","DOI":"10.3390/ijerph110808399","ISSN":"1660-4601","note":"PMID: 25153468\nPMCID: PMC4143868","journalAbbreviation":"Int J Environ Res Public Health","language":"eng","author":[{"family":"Gao","given":"Xiaoqian"},{"family":"Wang","given":"Hong-Sheng"}],"issued":{"date-parts":[["2014",8,15]]}}}],"schema":""} 14, and immunological diseases ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"EZwYFGf1","properties":{"formattedCitation":"\\super 15\\nosupersub{}","plainCitation":"15","noteIndex":0},"citationItems":[{"id":2704,"uris":[""],"uri":[""],"itemData":{"id":2704,"type":"webpage","title":"Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI. - PubMed - NCBI","abstract":"Reprod Toxicol. 2016 Oct;65:448-456. doi: 10.1016/j.reprotox.2016.06.020. Epub 2016 Jun 25.","URL":"","language":"en","author":[{"family":"Hessel","given":"EV"}],"issued":{"date-parts":[["2016"]]},"accessed":{"date-parts":[["2019",2,7]]}}}],"schema":""} 15. Numerous studies also suggest that BPA exposure has the potential to cause adverse behavioral and developmental effects in children ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"wzuyZ9VO","properties":{"formattedCitation":"\\super 16\\nosupersub{}","plainCitation":"16","noteIndex":0},"citationItems":[{"id":2225,"uris":[""],"uri":[""],"itemData":{"id":2225,"type":"article-journal","title":"Bisphenol A and human health: A review of the literature","container-title":"Reproductive Toxicology","page":"132-155","volume":"42","source":"ScienceDirect","abstract":"There is growing evidence that bisphenol A (BPA) may adversely affect humans. BPA is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between BPA and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking BPA to human health; 53 published within the last year. This review outlines this body of literature, showing associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental BPA exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental BPA exposure can be harmful to humans, especially in regards to behavioral and other effects in children.","DOI":"10.1016/j.reprotox.2013.08.008","ISSN":"0890-6238","shortTitle":"Bisphenol A and human health","journalAbbreviation":"Reproductive Toxicology","author":[{"family":"Rochester","given":"Johanna R."}],"issued":{"date-parts":[["2013",12,1]]}}}],"schema":""} 16. Due to the endocrine disrupting properties of BPA, exposure in fetuses, infants, and children, as well as women of childbearing age, is of special concern. It is well documented that these groups may have an increased susceptibility to certain toxicants during development, and so exposure to these types of chemicals should be limited.Structural analogues of BPA, such as BPF and BPS, have also been shown to be endocrine disrupting chemicals and to be as hormonally active as BPA, indicating that these are not suitable chemical replacements for BPA in food packaging applications ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8gIQ9lCQ","properties":{"formattedCitation":"\\super 19,20\\nosupersub{}","plainCitation":"19,20","noteIndex":0},"citationItems":[{"id":166,"uris":[""],"uri":[""],"itemData":{"id":166,"type":"article-journal","title":"Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes","container-title":"Environmental Health Perspectives","page":"643-650","volume":"123","issue":"7","source":"PubMed Central","abstract":"Background\nIncreasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled “BPA-free.” Some of the chemical replacements, however, are also bisphenols and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes.\n\nObjectives\nThis review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA.\n\nMethods\nWe conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol.\n\nResults\nWe identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive end points, and enzyme expression.\n\nConclusions\nBased on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects.\n\nCitation\nRochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes. Environ Health Perspect 123:643–650; ","DOI":"10.1289/ehp.1408989","ISSN":"0091-6765","note":"PMID: 25775505\nPMCID: PMC4492270","shortTitle":"Bisphenol S and F","journalAbbreviation":"Environ Health Perspect","author":[{"family":"Rochester","given":"Johanna R."},{"family":"Bolden","given":"Ashley L."}],"issued":{"date-parts":[["2015",7]]}}},{"id":3744,"uris":[""],"uri":[""],"itemData":{"id":3744,"type":"article-journal","title":"A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives","container-title":"Toxicology","page":"152235","volume":"424","source":"ScienceDirect","abstract":"Recent studies report widespread usage or exposure to a variety of chemicals with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogues or derivatives. These have been detected in foodstuffs, house dust, environmental samples, human urine or blood, and consumer products. Compared to BPA, relatively little is known about potential toxicity of these compounds. This scoping review aimed to summarize the human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities. PubMed was searched from March 1, 2015 to January 5, 2019 and combined with the results obtained from literature searches conducted through March 23, 2015, in The National Toxicology Program’s Research Report 4 (NTP RR-04), “Biological Activity of Bisphenol A (BPA) Structural Analogues and Functional Alternatives”. Study details are presented in interactive displays using Tableau Public. In total, 5748 records were screened for inclusion. One hundred sixty seven studies were included from NTP RR-04 and 175 studies were included from the updated literature search through January 2019. In total, there are 22, 117, and 221 human epidemiological, experimental animal, or in vitro studies included. The most frequently studied BPA analogues are bisphenol S (BPS), bisphenol F (4,4-BPF), and bisphenol AF (BPAF). Notable changes in the literature since 2015 include the growing body of human epidemiological studies and in vivo studies conducted in zebrafish. Numerous new endpoints were also evaluated across all three evidence streams including diabetes, obesity, and oxidative stress. However, few studies have addressed endpoints such as neurodevelopmental outcomes or impacts on the developing mammary or prostate glands, which are known to be susceptible to disruption by BPA. Further, there remains a critical need for better exposure information in order to prioritize experimental studies. Moving forward, researchers should also ensure that full dose responses are performed for all main effects in order to support hazard and risk characterization efforts. The evidence gathered here suggests that hazard and risk characterizations should expand beyond BPA in order to consider BPA structural and functional analogues.","DOI":"10.1016/j.tox.2019.06.006","ISSN":"0300-483X","journalAbbreviation":"Toxicology","author":[{"family":"Pelch","given":"Katherine"},{"family":"Wignall","given":"Jessica A."},{"family":"Goldstone","given":"Alexandra E."},{"family":"Ross","given":"Pam K."},{"family":"Blain","given":"Robyn B."},{"family":"Shapiro","given":"Andrew J."},{"family":"Holmgren","given":"Stephanie D."},{"family":"Hsieh","given":"Jui-Hua"},{"family":"Svoboda","given":"Daniel"},{"family":"Auerbach","given":"Scott S."},{"family":"Parham","given":"Fredrick M."},{"family":"Masten","given":"Scott A."},{"family":"Walker","given":"Vickie"},{"family":"Rooney","given":"Andrew"},{"family":"Thayer","given":"Kristina A."}],"issued":{"date-parts":[["2019",8,1]]}}}],"schema":""} 19,20.Exposure and Presence in ProductsDiet is the main route of BPA exposure in humans. BPA may migrate out of can and lid liners into food and beverages, leading to dietary exposures. Many variables contribute to the migration rates of BPA, such as food and beverage pH, storage time, temperature, and fat content. Because epoxy-based liners represent such a large portion of the food packaging landscape, exposure to these chemicals is a potential problem for a significant proportion of the general population. Food and beverage cans are widely available in California. In 2011, the Can Manufacturers Institute estimated that 98 percent of Americans have canned foods in their kitchens, with an average of 24 cans per household ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"TpgXkqzY","properties":{"formattedCitation":"\\super 21\\nosupersub{}","plainCitation":"21","noteIndex":0},"citationItems":[{"id":3749,"uris":[""],"uri":[""],"itemData":{"id":3749,"type":"webpage","title":"Canned Foods Stocked In 98 Percent Of Americans' Kitchens","URL":"","author":[{"family":"CMI","given":""}],"issued":{"date-parts":[["2013"]]},"accessed":{"date-parts":[["2019",8,14]]}}}],"schema":""} 21. A 2012 survey based on a sample of 1,017 U.S. adults found that 90 percent of Americans depend to some extent on canned fruits and vegetables for part of their produce intake. Those who depend on food assistance programs may rely on canned fruits and vegetables for a significant portion of their produce consumption. The survey found that Americans consume 5.5 cans of fruits and vegetables on average per week, but those receiving food assistance through the Supplemental Nutrition Assistance Program and Women, Infant and Children programs consume an average of 7.1 cans of fruit and vegetables per week ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"yUjJdPyU","properties":{"formattedCitation":"\\super 22\\nosupersub{}","plainCitation":"22","noteIndex":0},"citationItems":[{"id":3751,"uris":[""],"uri":[""],"itemData":{"id":3751,"type":"webpage","title":"New Research Confirms Americans Depend on Canned Fruits and Vegetables | Can Manufacturers Institute","URL":"","author":[{"family":"CMI","given":""}],"issued":{"date-parts":[["2012"]]},"accessed":{"date-parts":[["2019",8,14]]}}}],"schema":""} 22. This suggests that individuals of lower socioeconomic status may have higher rates of exposure to BPA and its alternatives. As a result, this product-chemical combination addresses widespread exposure to the general population of California, as well as exposure within sensitive subpopulations (women and children).Next StepsPublic EngagementDTSC is asking stakeholders to address the questions listed in Themes 1-3 below. A public comment period will begin on November 19, 2019. Written comments can be submitted via the online information management system CalSAFER. The comment period will close on December 19, 2019, at 11:59 p.m. In addition, DTSC will hold a public workshop with stakeholders and invited participants on November 19, 2019. Further details about this workshop will be available on our Workshops and Events Webpage. This stakeholder engagement process will help inform additional research that may result in the proposal of one or more Priority Products. Please monitor our Priority Products Work Plan Implementation webpage for updates on this topic.Questions to StakeholdersTheme 1. ManufacturingWho manufacturers food packaging liners in the United States?Who manufactures food packaging that contains BPA and/or its alternatives?Are there any food packaging manufacturers in California that make products with BPA and/or its alternatives? What chemicals are currently used to manufacture can and lid liners in food packaging?What type of liners are California manufacturers using (epoxy-based, oleoresin, vinyl, phenolic, acrylic, polyester, polyolefins), and how do they differ by product subtype (food cans, beverage cans, jar lids, bottle caps)?Theme 2. Market PresenceHow much food packaging containing BPA and/or its alternatives, and what types, are on the market in California and nationally?Which manufacturers supply the liners used in food and beverage cans sold in California?Do you have any specific data on the market presence of food packaging containing BPA and/or its alternatives and the supply chain?Theme 3. Supply ChainWho manufactures and supplies the BPA and/or its alternatives-containing starting materials (e.g., epoxy-based liners) to food packaging manufacturers?Are there intermediaries (converters) who take the liner materials (e.g., liner materials) and assemble them into a more final food package product (ex. food or beverage can), and who are they?Are there manufacturers of food packaging liners that contain BPA and/or its alternatives located outside the United States, and if so who are they and where are they located? Are these products imported to the United States and/or sold in California?References ADDIN ZOTERO_BIBL {"uncited":[],"omitted":[],"custom":[]} CSL_BIBLIOGRAPHY 1.DTSC, (Department of Toxic Substances Control). 2018-2020 Priority Product Work Plan. Available at: . (Accessed: 7th August 2019)2.Rubin, B. S. Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects. The Journal of Steroid Biochemistry and Molecular Biology 127, 27–34 (2011).3.Rochester, J. R., Bolden, A. L. & Kwiatkowski, C. F. Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis. Environ Int 114, 343–356 (2018).4.Perera, F. et al. Prenatal bisphenol a exposure and child behavior in an inner-city cohort. Environ. Health Perspect. 120, 1190–1194 (2012).5.Hong, S.-B. et al. Bisphenol A in relation to behavior and learning of school-age children. J Child Psychol Psychiatry 54, 890–899 (2013).6.Braun, J. M. et al. Impact of Early-Life Bisphenol A Exposure on Behavior and Executive Function in Children. PEDIATRICS 128, 873–882 (2011).7.Ejaredar, M., Lee, Y., Roberts, D. J., Sauve, R. & Dewey, D. Bisphenol A exposure and children’s behavior: A systematic review. Journal of Exposure Science & Environmental Epidemiology 27, 175–183 (2017).8.Ziv-Gal, A. & Flaws, J. A. Evidence for bisphenol A-induced female infertility: a review (2007-2016). Fertil. Steril. 106, 827–856 (2016).9.Wetherill, Y. B. et al. In vitro molecular mechanisms of bisphenol A action. Reprod. Toxicol. 24, 178–198 (2007).10.Teng, C. et al. Bisphenol A affects androgen receptor function via multiple mechanisms. Chem. Biol. Interact. 203, 556–564 (2013).11.MacKay, H. & Abizaid, A. A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA). Horm Behav 101, 59–67 (2018).12.Alonso-Magdalena, P., Rivera, F. J. & Guerrero-Bosagna, C. Bisphenol-A and metabolic diseases: epigenetic, developmental and transgenerational basis. Environ Epigenet 2, dvw022 (2016).13.Hugo, E. R. et al. Bisphenol A at Environmentally Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes. Environmental Health Perspectives 116, 1642–1647 (2008).14.Gao, X. & Wang, H.-S. Impact of bisphenol a on the cardiovascular system - epidemiological and experimental evidence and molecular mechanisms. Int J Environ Res Public Health 11, 8399–8413 (2014).15.Hessel, E. Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI. - PubMed - NCBI. (2016). Available at: . (Accessed: 7th February 2019)16.Rochester, J. R. Bisphenol A and human health: A review of the literature. Reproductive Toxicology 42, 132–155 (2013).17.Wolstenholme, J. T., Rissman, E. F. & Connelly, J. J. The role of Bisphenol A in shaping the brain, epigenome and behavior. Horm Behav 59, 296–305 (2011).18.Prins, G. S., Patisaul, H. B., Belcher, S. M. & Vandenberg, L. N. CLARITY-BPA academic laboratory studies identify consistent low-dose Bisphenol A effects on multiple organ systems. Basic Clin. Pharmacol. Toxicol. (2018). doi:10.1111/bcpt.1312519.Rochester, J. R. & Bolden, A. L. Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes. Environ Health Perspect 123, 643–650 (2015).20.Pelch, K. et al. A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives. Toxicology 424, 152235 (2019).21.CMI. Canned Foods Stocked In 98 Percent Of Americans’ Kitchens. (2013). Available at: . (Accessed: 14th August 2019)22.CMI. New Research Confirms Americans Depend on Canned Fruits and Vegetables | Can Manufacturers Institute. (2012). Available at: . (Accessed: 14th August 2019) ................
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