Dataset Information

Comparison of serum bisphenol A concentrations in mice exposed to bisphenol A through the diet versus oral bolus exposure.

ABSTRACT:

Background

Bisphenol A (BPA) is a widely produced endocrine-disrupting chemical. Diet is a primary route of exposure, but internal exposure (serum concentrations) in animals and humans has been measured only after single oral bolus administration.

Objective

We compared serum concentrations of BPA over a 24-hr period after oral bolus administration or ad libitum feeding in mice and assessed for buildup with dietary exposure.

Methods

Adult female mice were administered [dimethyl-d6]-BPA (BPA-d6) as a single oral bolus (20 mg/kg body weight) or fed a diet containing 100 mg BPA-d6/kg feed weight ad libitum for 1 week. Serum concentrations were analyzed using isotope dilution liquid chromatography coupled with electrospray tandem mass spectrometry and compared between exposure groups over the first 23 hr and after 7 days of dietary exposure.

Results

Maximum concentration (Cmax) for BPA-d6 during the first 24 hr was reached at 1 hr and 6 hr for oral bolus and diet groups, respectively. Relative BPA-d6 bioavailability (unconjugated BPA-d6) was higher in diet-exposed mice than in the bolus group despite a relative lower absorption, a phenomenon consistent with an inhibitory effect of food on first-pass hepatic metabolism. In mice with ongoing dietary exposure, unconjugated BPA-d6 was higher on day 7 than on day 1.

Conclusions

This is the first report of serum BPA concentrations in an animal model exposed to this chemical via the diet. Although bolus administration of BPA-d6 led to peak concentrations within 1 hr, Cmax for diet-exposed mice was delayed for several hours. However, bolus administration underestimates bioavailable serum BPA concentrations in animals-and presumably humans-than would result from dietary exposure. Exposure via diet is a more natural continuous exposure route than oral bolus exposure and is thus a better predictor of BPA concentrations in chronically exposed animals and humans.

SUBMITTER: Sieli PT

PROVIDER: S-EPMC3230401 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Publications

Comparison of serum bisphenol A concentrations in mice exposed to bisphenol A through the diet versus oral bolus exposure.

Sieli Paizlee T PT Jašarevic Eldin E Warzak Denise A DA Mao Jiude J Ellersieck Mark R MR Liao Chunyang C Kannan Kurunthachalam K Collet Séverine H SH Toutain Pierre-Louis PL Vom Saal Frederick S FS Rosenfeld Cheryl S CS

Environmental health perspectives 20110606 9

<h4>Background</h4>Bisphenol A (BPA) is a widely produced endocrine-disrupting chemical. Diet is a primary route of exposure, but internal exposure (serum concentrations) in animals and humans has been measured only after single oral bolus administration.<h4>Objective</h4>We compared serum concentrations of BPA over a 24-hr period after oral bolus administration or ad libitum feeding in mice and assessed for buildup with dietary exposure.<h4>Methods</h4>Adult female mice were administered [dimet ...[more]

PMID: 21642047

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Project description:Perfluorinated compounds (PFCs) have emerged as important food contaminants. They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood.To determine whether PFC exposure is associated with antibody response to childhood vaccinations.Prospective study of a birth cohort from the National Hospital in the Faroe Islands. A total of 656 consecutive singleton births were recruited during 1997-2000, [corrected] and 587 participated in follow-up through 2008.Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years.Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of -39% (95% CI, -55% to -17%) in the diphtheria antibody concentration. PFCs in the child's serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant. In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of -49% (95% CI, -67% to -23%) in the overall antibody concentration. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 2.38 (95% CI, 0.89 to 6.35) and 4.20 (95% CI, 1.54 to 11.44) for falling below a clinically protective level of 0.1 IU/mL for tetanus and diphtheria antibodies at age 7 years.Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.

Project description:BackgroundBisphenol A (BPA) is an endocrine disruptor and potential reproductive toxicant, but results of epidemiologic studies have been mixed and have been criticized for inadequate exposure assessment that often relies on a single measurement.ObjectiveOur goal was to describe the distribution of BPA concentrations in serial urinary specimens, assess temporal variability, and provide estimates of exposure classification when randomly selected samples are used to predict average exposure.MethodsWe collected and analyzed 2,614 urine specimens from 83 Utah couples beginning in 2012. Female participants collected daily first-morning urine specimens during one to two menstrual cycles and male partners collected specimens during the woman's fertile window for each cycle. We measured urinary BPA concentrations and calculated geometric means (GM) for each cycle, characterized the distribution of observed values and temporal variability using intraclass correlation coefficients, and performed surrogate category analyses to determine how well repeat samples could classify exposure.ResultsThe GM urine BPA concentration was 2.78 ng/mL among males and 2.44 ng/mL among females. BPA had a high degree of variability among both males (ICC = 0.18; 95% CI: 0.11, 0.26) and females (ICC = 0.11; 95% CI: 0.08, 0.16). Based on our more stringent surrogate category analysis, to reach proportions ≥ 0.80 for sensitivity, specificity, and positive predictive value (PPV) among females, 6 and 10 repeat samples for the high and low tertiles, respectively, were required. For the medium tertile, specificity reached 0.87 with 10 repeat samples, but even with 11 samples, sensitivity and PPV did not exceed 0.36. Five repeat samples, among males, yielded sensitivity and PPV values ≥ 0.75 for the high and low tertiles, but, similar to females, classification for the medium tertile was less accurate.ConclusionRepeated urinary specimens are required to characterize typical BPA exposure.CitationCox KJ, Porucznik CA, Anderson DJ, Brozek EM, Szczotka KM, Bailey NM, Wilkins DG, Stanford JB. 2016. Exposure classification and temporal variability in urinary bisphenol A concentrations among couples in Utah-the HOPE study. Environ Health Perspect 124:498-506; http://dx.doi.org/10.1289/ehp.1509752.

Dataset Information

Comparison of serum bisphenol A concentrations in mice exposed to bisphenol A through the diet versus oral bolus exposure.

Background

Objective

Methods

Results

Conclusions

Publications

Comparison of serum bisphenol A concentrations in mice exposed to bisphenol A through the diet versus oral bolus exposure.

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