Judy S. LaKind

Daily intake of bisphenol A and potential sources of exposure: 2005–2006 National Health and Nutrition Examination Survey

Nationally representative data on urinary levels of bisphenol A (BPA) and its metabolites in the United States from the 2005–2006 National Health and Nutrition Examination Survey (NHANES) were used to estimate daily BPA intakes. In addition, NHANES data on potential sources of BPA exposure and personal characteristics were explored for their association with urinary BPA levels. On the basis of 2005–2006 NHANES urinary BPA data and assumptions described in this paper, median daily intake for the overall population is approximately 34 ng/kg-day. Median daily BPA intakes for men are statistically significantly higher than for women; there is a significant decrease in daily BPA intake with increasing age. Gender- and age-specific median intakes differ from the overall population by less than a factor of 2. Although estimates of daily BPA intake have decreased compared with those from the 2003–2004 NHANES, it is premature to draw conclusions regarding trends at this time, as there is no indication that BPA use declined from 2003 to 2006. On the basis of an assessment of urinary BPA and questionnaire data from the 2005–2006 NHANES, consumption of soda, school lunches, and meals prepared outside the home — but not bottled water or canned tuna — was statistically significantly associated with higher urinary BPA.

Bisphenol A (BPA) daily intakes in the United States: Estimates from the 2003–2004 NHANES urinary BPA data

Investigations into human exposure to bisphenol A (BPA) have, for the most part, assessed intake based on food consumption estimates combined with measurements or estimates of BPA in foods. In this study, nationally representative data on urinary levels of BPA in the United States (US) from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) were used to estimate daily intake of BPA, assuming steady-state excretion. Distributions of intakes for the US population were determined for (i) all NHANES participants with urinary BPA data; (ii) participants by the following age groups: 6–11 years, 12–19 years, 20–39 years, 40–59 years, and 60+ years; and (iii) participants by gender. On the basis of the NHANES urinary BPA data and the assumptions described in this paper, daily BPA intakes for male participants are statistically significantly higher than for female participants, and there are statistically significant differences in daily BPA intakes according to age groups, with the oldest group having the lowest estimated intakes. Median intake was approximately three orders of magnitude below health-based guidance values of 50 μg/kg-day.

Guidelines for the communication of Biomonitoring Equivalents: Report from the Biomonitoring Equivalents Expert Workshop

Biomonitoring Equivalents (BEs) are screening tools for interpreting biomonitoring data. However, the development of BEs brings to the public a relatively novel concept in the field of health risk assessment and presents new challenges for environmental risk communication. This paper provides guidance on methods for conveying information to the general public, the health care community, regulators and other interested parties regarding how chemical-specific BEs are derived, what they mean in terms of health, and the challenges and questions related to interpretation and communication of biomonitoring data. Key communication issues include: (i) developing a definition of the BE that accurately captures the BE concept in lay terms, (ii) how to compare population biomonitoring data to BEs, (iii) interpreting biomonitoring data that exceed BEs for a specific chemical, (iv) how to best describe the confidence in chemical-specific BEs, and (v) key requirements for effective communication with health care professionals. While the risk communication literature specific to biomonitoring is sparse, many of the concepts developed for traditional risk assessments apply, including transparency and discussions of confidence and uncertainty. Communication of BEs will require outreach, education, and development of communication materials specific to several audiences including the lay public and health care providers.

Childhood asthma and environmental exposures at swimming pools: state of the science and research recommendations.

Objectives Recent studies have explored the potential for swimming pool disinfection by-products (DBPs), which are respiratory irritants, to cause asthma in young children. Here we describe the state of the science on methods for understanding children’s exposure to DBPs and biologics at swimming pools and associations with new-onset childhood asthma and recommend a research agenda to improve our understanding of this issue. Data sources A workshop was held in Leuven, Belgium, 21–23 August 2007, to evaluate the literature and to develop a research agenda to better understand children’s exposures in the swimming pool environment and their potential associations with new-onset asthma. Participants, including clinicians, epidemiologists, exposure scientists, pool operations experts, and chemists, reviewed the literature, prepared background summaries, and held extensive discussions on the relevant published studies, knowledge of asthma characterization and exposures at swimming pools, and epidemiologic study designs. Synthesis Childhood swimming and new-onset childhood asthma have clear implications for public health. If attendance at indoor pools increases risk of childhood asthma, then concerns are warranted and action is necessary. If there is no such relationship, these concerns could unnecessarily deter children from indoor swimming and/or compromise water disinfection. Conclusions Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive. Important data gaps need to be filled, particularly in exposure assessment and characterization of asthma in the very young. Participants recommended that additional evaluations using a multidisciplinary approach are needed to determine whether a clear association exists.

A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects

Abstract Biomarkers associated with asthma aetiology and exacerbation have been sought to shed light on this multifactorial disease. One candidate is the serum concentration of the Clara cell secretory protein (CC16, sometimes referred to as CC10 or uteroglobin). In this review, we examine serum CC16s relation to asthma aetiology and exacerbation. There is evidence that acute exposures to certain pulmonary irritants can cause a transient increase in serum CC16 levels, and limited evidence also suggests that a transient increase in serum CC16 levels can be caused by a localized pulmonary inflammation. Research also indicates that a transient increase in serum CC16 is not associated with measurable pulmonary damage or impairment of pulmonary function. The biological interpretation of chronic changes in serum CC16 is less clear. Changes in serum CC16 concentrations (either transient or chronic) are not specific to any one agent, disease state, or aetiology. This lack of specificity limits the use of serum CC16 as a biomarker of specific exposures. To date, many of the critical issues that must be understood before serum CC16 levels can have an application as a biomarker of effect or exposure have not been adequately addressed.

Do human milk concentrations of persistent organic chemicals really decline during lactation? Chemical concentrations during lactation and milk/serum partitioning.

Background Conventional wisdom regarding exposures to persistent organic chemicals via breast-feeding assumes that concentrations decline over the course of lactation and that the mother’s body burden reflects her cumulative lifetime exposure. Two important implications stemming from these lines of thought are, first, that assessments of early childhood exposures should incorporate decreasing breast milk concentrations over lactation; and, second, that there is little a breast-feeding mother can do to reduce her infant’s exposures via breast-feeding because of the cumulative nature of these chemicals. Objectives We examined rates of elimination and milk/serum partition coefficients for several groups of persistent organic chemicals. Methods We collected simultaneous milk and blood samples of 10 women at two times postpartum and additional milk samples without matching blood samples. Results Contrary to earlier research, we found that lipid-adjusted concentrations of polybrominated diphenyl ethers, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and furans, and organochlorine pesticides in serum and milk do not consistently decrease during lactation and can increase for some women. Published research has also suggested an approximate 1:1 milk/serum relationship (lipid adjusted) on a population basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin; however, our results suggest a more complex relationship for persistent, lipophilic chemicals with the milk/serum relationship dependent on chemical class. Conclusions Decreases in concentration of lipophilic chemicals on a lipid-adjusted basis during lactation should no longer be assumed. Thus, the concept of pumping and discarding early milk as means of reducing infant exposure is not supported. The hypothesis that persistent lipophilic chemicals, on a lipid-adjusted basis, have consistent concentrations across matrices is likely too simplistic.

Bisphenol A and indicators of obesity, glucose metabolism/type 2 diabetes and cardiovascular disease: A systematic review of epidemiologic research

Abstract Introduction: Bisphenol A (BPA), a high-volume chemical with weak estrogenic properties, has been linked to obesity, cardiovascular diseases (CVD) and diabetes mellitus (DM). This review evaluates both the consistency and the quality of epidemiological evidence from studies testing the hypothesis that BPA exposure is a risk factor for these health outcomes. Methods: We followed the current methodological guidelines for systematic reviews by using two independent researchers to identify, review and summarize the relevant epidemiological literature on the relation of BPA to obesity, CVD, DM, or related biomarkers. Each paper was summarized with respect to its methods and results with particular attention to study design and exposure assessment, which have been cited as the main areas of weakness in BPA epidemiologic research. As quantitative meta-analysis was not feasible, the study results were categorized qualitatively as positive, inverse, null, or mixed. Results: Nearly all studies on BPA and obesity-, DM- or CVD-related health outcomes used a cross-sectional design and relied on a single measure of BPA exposure, which may result in serious exposure misclassification. For all outcomes, results across studies were inconsistent. Although several studies used the same data and the same or similar statistical methods, when the methods varied slightly, even studies that used the same data produced different results. Conclusion: Epidemiological study design issues severely limit our understanding of health effects associated with BPA exposure. Considering the methodological limitations of the existing body of epidemiology literature, assertions about a causal link between BPA and obesity, DM, or CVD are unsubstantiated.

Use of NHANES Data to Link Chemical Exposures to Chronic Diseases: A Cautionary Tale

Background The National Health and Nutrition Examination Survey (NHANES) is one example of cross-sectional datasets that have been used to draw causal inferences regarding environmental chemical exposures and adverse health outcomes. Our objectives were to analyze four NHANES datasets using consistent a priori selected methods to address the following questions: Is there a consistent association between urinary bisphenol A (BPA) measures and diabetes, coronary heart disease (CHD), and/or heart attack across surveys? Is NHANES an appropriate dataset for investigating associations between chemicals with short physiologic half-lives such as BPA and chronic diseases with multi-factorial etiologies? Data on urinary BPA and health outcomes from 2003–2004, 2005–2006, 2007–2008, and 2009–2010 were available. Methodology and Findings Regression models were adjusted for creatinine, age, gender, race/ethnicity, education, income, smoking, heavy drinking, BMI, waist circumference, calorie intake, family history of heart attack, hypertension, sedentary time, and total cholesterol. Urinary BPA was not significantly associated with adverse health outcomes for any of the NHANES surveys, with ORs (95% CIs) ranging from 0.996 (0.951–1.04) to 1.03 (0.978–1.09) for CHD, 0.987 (0.941–1.04) to 1.04 (0.996–1.09) for heart attack, and 0.957 (0.899–1.02) to 1.01 (0.980–1.05) for diabetes. Conclusions Using scientifically and clinically supportable exclusion criteria and outcome definitions, we consistently found no associations between urinary BPA and heart disease or diabetes. These results do not support associations and causal inferences reported in previous studies that used different criteria and definitions. We are not drawing conclusions regarding whether BPA is a risk factor for these diseases. We are stating the opposite–that using cross-sectional datasets like NHANES to draw such conclusions about short-lived environmental chemicals and chronic complex diseases is inappropriate. We need to expend resources on appropriately designed epidemiologic studies and toxicological explorations to understand whether these types of chemicals play a causal role in chronic diseases.

METHODOLOGY FOR CHARACTERIZING DISTRIBUTIONS OF INCREMENTAL BODY BURDENS OF 2,3,7,8-TCDD AND DDE FROM BREAST MILK IN NORTH AMERICAN NURSING INFANTS

A clear picture of ranges of doses of breast-milk contaminants experienced by nursing infants in North America has not yet been described, resulting in a significant gap in our understanding of potential health risks to infants from those contaminants. While point estimates of incremental dose have appeared in the published literature, these do not account for the wide variability in exposures experienced by nursing infants. This research expands on the current state of understanding of breast-milk contaminant exposure by characterizing distributions, rather than point estimates, of dose. Distributions of milk intake by nursing infants were characterized to examine intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and dichlorodiphenyl dichloroethane (DDE). The results indicate that, despite the uncertainties inherent in modeling incremental body burdens of chemicals from nursing, estimating incremental infant body burdens of lipophilic chemicals from breastfeeding using point estimates may result in overly conservative estimates of the contribution of breastfeeding to long-term body burdens of those chemicals in children. To develop reliable estimates of incremental body burden from nursing, depuration via lactation and half-life in the infant should be considered. Further, incremental infant body burdens of lipophilic chemicals increase rapidly at the start of lactation, but decrease after approximately 5 to 6 mo; by 2 yr postpartum, incremental body burdens have decreased substantially. Given the benefits afforded to infants who breastfeed, and because breastfeeding does not necessarily lead to significantly increased long-term body burdens in infants, breastfeeding should be encouraged and promoted.

The Good, the Bad, and the Volatile: Can We Have Both Healthy Pools and Healthy People?

Swimming is a healthful activity that comes with increased risk of exposure to pathogenic microorganisms and disinfection agents/byproducts.