Urinary bisphenol a concentration and angiography-defined coronary artery stenosis.

BACKGROUND: Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses. METHODOLOGY/PRINCIPAL FINDINGS: To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n=86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD=5.96 ng/ml OR=1.43, CI 1.03 to 1.98, p=0.033), and near significant for intermediate disease (OR=1.69, CI 0.98 to 2.94, p=0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined. CONCLUSIONS/SIGNIFICANCE: BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established.

Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women.

BACKGROUND: The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors. METHODS AND RESULTS: We included 758 incident coronary artery disease (CAD) cases and 861 controls followed for 10.8 years from the European Prospective Investigation of Cancer-Norfolk UK. Respondents aged 40 to 74 years and free of CAD, stroke, or diabetes mellitus provided baseline spot urine samples. Urinary BPA concentrations (median value, 1.3 ng/mL) were low. Per-SD (4.56 ng/mL) increases in urinary BPA concentration were associated with incident CAD in age-, sex-, and urinary creatinine-adjusted models (n=1919; odds ratio=1.13; 95% confidence interval, 1.02-1.24; P=0.017). With CAD risk factor adjustment (including education, occupational social class, body mass index category, systolic blood pressure, lipid concentrations, and exercise), the estimate was similar but narrowly missed 2-sided significance (n=1744; odds ratio=1.11; 95% confidence interval, 1.00-1.23; P=0.058). Sensitivity analyses with the fully adjusted model, excluding those with early CAD (<3-year follow-up), body mass index >30, or abnormal renal function or with additional adjustment for vitamin C, C-reactive protein, or alcohol consumption, all produced similar estimates, and all showed associations at P≤0.05. CONCLUSIONS: Associations between higher BPA exposure (reflected in higher urinary concentrations) and incident CAD during >10 years of follow-up showed trends similar to previously reported cross-sectional findings in the more highly exposed NHANES respondents. Further work is needed to accurately estimate the prospective exposure-response curve and to establish the underlying mechanisms.

Bisphenol A exposure is associated with in vivo estrogenic gene expression in adults.

BACKGROUND: Bisphenol A (BPA) is a synthetic estrogen commonly used in polycarbonate plastic and resin-lined food and beverage containers. Exposure of animal and cell models to doses of BPA below the recommended tolerable daily intake (TDI) of 50 µg/kg/day have been shown to alter specific estrogen-responsive gene expression, but this has not previously been shown in humans. OBJECTIVE: We investigated associations between BPA exposure and in vivo estrogenic gene expression in humans. METHODS: We studied 96 adult men from the InCHIANTI population study and examined in vivo expression of six estrogen receptor, estrogen-related receptor, and androgen receptor genes in peripheral blood leukocytes. RESULTS: The geometric mean urinary BPA concentration was 3.65 ng/mL [95% confidence interval (CI): 3.13, 4.28], giving an estimated mean excretion of 5.84 µg/day (95% CI: 5.00, 6.85), significantly below the current TDI. In age-adjusted models, there were positive associations between higher BPA concentrations and higher ESR2 [estrogen receptor 2 (ER beta)] expression (unstandardized linear regression coefficient = 0.1804; 95% CI: 0.0388, 0.3221; p = 0.013) and ESRRA (estrogen related receptor alpha) expression (coefficient = 0.1718; 95% CI: 0.0213, 0.3223; p = 0.026): These associations were little changed after adjusting for potential confounders, including obesity, serum lipid concentrations, and white cell subtype percentages. Upper-tertile BPA excretors (urinary BPA > 4.6 ng/mL) had 65% higher mean ESR2 expression than did lower-tertile BPA excretors (0-2.4 ng/mL). CONCLUSIONS: Because activation of nuclear-receptor-mediated pathways by BPA is consistently found in laboratory studies, such activation in humans provides evidence that BPA is likely to function as a xenoestrogen in this sample of adults.

Metal speciation and toxicity of Tamar Estuary water to larvae of the Pacific oyster, Crassostrea gigas.

As part of the PREDICT Tamar Workshop, the toxicity of estuarine waters in the Tamar Estuary (southwest England) was assessed by integration of metal speciation determination with bioassays. High temporal resolution metal speciation analysis was undertaken in situ by deployment of a Voltammetric In situ Profiling (VIP) system. The VIP detects Cd (cadmium), Pb (lead) and Cu (copper) species smaller than 4 nm in size and this fraction is termed 'dynamic' and considered biologically available. Cadmium was mainly present in the dynamic form and constituted between 56% and 100% of the total dissolved concentration, which was determined subsequently in the laboratory in filtered discrete samples. In contrast, the dynamic Pb and Cu fractions were less important, with a much larger proportion of these metals associated with organic ligands and/or colloids (45-90% Pb and 46-85% Cu), which probably reduced the toxicological impact of these elements in this system. Static toxicity tests, based on the response of Crassostrea gigas larva exposed to discrete water samples showed a high level of toxicity (up to 100% abnormal development) at two stations in the Tamar, particularly during periods of the tidal cycle when the influence of more pristine coastal water was at its lowest. Competitive ligand-exchange Cu titrations showed that natural organic ligands reduced the free cupric ion concentration to levels that were unlikely to have been the sole cause of the observed toxicity. Nonetheless, it is probable that the combined effect of the metals determined in this work contributed significantly to the bioassay response.

Daily bisphenol A excretion and associations with sex hormone concentrations: results from the InCHIANTI adult population study.

BACKGROUND: Bisphenol A (BPA) is a high production volume chemical widely used in packaging for food and beverages. Numerous studies have demonstrated that BPA can alter endocrine function in animals, yet human studies remain limited. OBJECTIVE: We estimated daily excretion of BPA among adults and examined hypothesized associations with serum estrogen and testosterone concentrations. METHODS: We conducted cross-sectional analyses using data from the InCHIANTI Study, a prospective population-based study of Italian adults. Our study included 715 adults between 20 and 74 years old. BPA concentrations were measured by liquid chromatography-mass spectrometry in 24-hr urine samples. The main outcome measures were serum concentrations of total testosterone and 17beta-estradiol. RESULTS: Geometric mean urinary BPA concentration was 3.59 ng/mL [95% confidence interval (CI), 3.42-3.77 ng/mL], and mean excretion was 5.63 microg/day (5th population percentile, 2.1 microg/day; 95th percentile, 16.4 microg/day). We found higher excretion rates among men, younger respondents, and those with increasing waist circumference (p = 0.013) and weight (p = 0.003). Higher daily BPA excretion was associated with higher total testosterone concentrations in men, in models adjusted for age and study site (p = 0.044), and in models additionally adjusted for smoking, measures of obesity, and urinary creatinine concentrations (beta = 0.046; 95% CI, 0.015-0.076; p = 0.004). We found no associations with the other serum measures. We also found no associations with the primary outcomes among women, but we did find an association between BPA and SHBG concentrations in the 60 premenopausal women. CONCLUSION: Higher BPA exposure may be associated with endocrine changes in men. The mechanisms involved in the observed cross-sectional association with total testosterone concentrations need to be clarified.