Butylparaben (Butyl p-hydroxybenzoic acid) is a widely used cosmetic and pharmaceutical preservative that has been recently shown to induce oxidative stress and have endocrine disrupting effects in rodents, and promote adipocyte conversion of human adipose cells. Embryonic development is extremely sensitive to oxidative stress due to changes in cell growth, development and differentiation that occur during this life stage. Fluctuations in redox potentials play critical roles in normal embryonic development by guiding these cell signaling, cell-fate decisions and apoptosis. The most prevalent endogenous antioxidant that defends against oxidative stress is glutathione (GSH), which scavenges reactive oxygen species. The low antioxidant capacity of pancreatic beta cells suggests that they are sensitive target tissues of oxidative stress; this has yet to be investigated during embryonic development. Here, we aim to 1) determine whether embryonic exposure to butylparaben prompts structural and functional changes in the developing endocrine pancreas and 2) determine whether oxidative stress may be involved. Transgenic insulin-GFP zebrafish embryos were treated daily with 250, 500, 1,000 and 3,000 nM butylparaben starting at 3 hours post fertilization (hpf). Pancreatic islet and whole embryo morphological development were examined daily until 7 days post fertilization (dpf). Redox potentials were measured at 24 and 28 hpf using HPLC. Area of the pancreatic islet increased over time with increasing butylparaben exposure in a dose-dependent manner by as much as a 55% increase in islet area at 3 dpf when compared to controls. Butylparaben concentrations of 500 and 1,000 nM increased GSH by 10 and 40%, respectively, and decreased oxidized glutathione disulfide by 37 and 59%. GSH redox potentials were only significant in embryos collected at 28 hpf and became more reduced with 500 and 1,000 nM butylparaben exposure, decreasing redox potentials by 7 and 18 mV, respectively. Cysteine redox potentials also became more reduced, decreasing by 17 and 28 mV. Our data show that butylparaben-induced redox potential disruptions that may be responsible for the effects on pancreatic islet structure and function, but further studies are needed to determine how and if that directly affects pancreas development.

Background: Paraben exposure occurs everyday to most people unknowingly. Parabens are present in most personal care products in varying amounts. Presently, parabens are not listed as endocrine disruptors; however, some research has shown parabens associated with decreases in thyroid hormone levels. The chemical and adsorption mechanism for parabens in association with thyroid hormones is not well understood. Determining whether parabens are associated with a change in thyroid hormone levels can help reduce the incidence of possible adverse health effects with exposure to parabens. Methodology: The selected study variables were analyzed using SAS version 9.2. Data were obtained from the 2007-2008 National Health and Nutrition Examination Survey (NHANES). Analyses were performed separately for adolescent females (12-19) and adult females (20+). Weighted means were performed for the main independent and dependent variables of interest stratified by race/ethnicity groups and by smoking status. Independent samples t-test and ANOVA was used to test significance of differences of weighted means. Weighted bivariate linear regression was performed for each dependent variable (Thyroid Stimulating Hormone [TSH], Triiodothyronine [T3], and Thyroxine [T4]) regressed on butylparaben. Weighted multiple linear regressions were performed and parameter estimates with 95% confidence intervals were used to ascertain the measure of effect. Separate regression models stratified by age group (adolescent vs. adult) were ran for each dependent variable (TSH, T3, and T4) regressed on butylparaben level and covariates, race/ethnicity and smoking status (ever smoked). Results: Weighted bivariate linear regression showed that among adult females, for each ng/ml increase in butylparaben, there was a -1.07 decrease in ng/dL T3 (p Weighted multiple linear regression showed higher butylparaben levels among adult females were associated with 0.12 ug/dL lower than average T4 levels (p Conclusion: While parabens are currently not considered endocrine disruptors, the human metabolism of and effects from exposure to parabens are not well understood. Results from this study showing decreased levels of some thyroid hormone levels (TSH, T3, and T4) associated with increased levels of butylparaben was found, as well as differences in thyroid hormone levels among racial/ethnic groups. Although not many human studies have found significant results, 10 some rodent studies have found butylparaben associations with thyroid hormone changes.4, 6, 19, 54 The results of this study indicating no statistically significant association between butylparaben and decreases in thyroid hormone levels are consistent with results of some rodent studies.7, 8, 54, 55 In light of these findings, additional human studies with paraben exposure and thyroid hormone levels are needed to increase knowledge of the mechanism and effect of parabens in the human body.