Fate of five bisphenol derivatives in Chlamydomonas mexicana: Toxicity, removal, biotransformation and microalgal metabolism.

Bisphenols (BPs) are recognized as emerging contaminants because of their estrogenic properties and frequent occurrence in environmental matrices. Here, we evaluated the toxic effects of five common BPs on freshwater microalga Chlamydomonas mexicana and removal of the BPs by the alga. Bisphenols -AF (BPAF), -B (BPB), and -Z (BPZ) (96 h, EC50 1.78-12.09 mg·L-1) exhibited higher toxicity to C. mexicana compared to bisphenol -S (BPS) and -F (BPF) (96 h, EC50 30.53-85.48 mg·L-1). In contrast, the mixture of BPs exhibited acute toxicity (96 h, EC50 8.07 mg·L-1). After 14 days, C. mexicana had effectively removed 61%, 99%, 55%, 87%, and 89% of BPS, BPF, BPAF, BPB, and BPZ, respectively, at 1 mg L-1. The biotransformed products of all five BPs were analyzed using UHPLC QTOF, and their toxicity was predicted. All biotransformed products were observed to be less toxic than the parent compounds. The fatty acid composition of C. mexicana after exposure to the BP mixture was predominantly palmitic acid (34.14%), followed by oleic acid (18.9%), and γ-linolenic acid (10.79%). The results provide crucial information on the ecotoxicity of these five BPs and their removal by C. mexicana; the resulting biomass is a potential feedstock for producing biodiesel.

Association of Serum Levels of Plasticizers Compounds, Phthalates and Bisphenols, in Patients and Survivors of Breast Cancer: A Real Connection?

Phthalates and bisphenols are ubiquitous environmental pollutants with the ability to perturb different systems. Specifically, they can alter the endocrine system, and this is why they are also known as endocrine-disrupting compounds (EDCs). Interestingly, they are related to the development and progression of breast cancer (BC), but the threshold concentrations at which they trigger that are not well established. OBJECTIVES: The aim of this study was to compare the concentration measures of parent EDCs in three groups of women (without BC, with BC, and BC survivors) from two urban populations in Mexico, to establish a possible association between EDCs and this disease. We consider the measure of the parent compounds would reflect the individual's exposure. METHODS: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP) and di-ethyl-phthalate (DEP), bisphenol A (BPA) and bisphenol S (BPS) were determined by gas chromatograph-mass spectrometry in 102 subjects, including 37 women without any pathological disease, 46 patients with BC and 19 women survivals of BC of Mexico and Toluca City. RESULTS: All phthalates were detected in 100% of women, two of them were significantly higher in patients with different BC subtypes in Mexico City. Differential increases were observed mainly in the serum concentration of phthalates in women with BC compared to women without disease between Mexico and Toluca City. In addition, when performing an analysis of the concentrations of phthalates by molecular type of BC, DEP and BBP were found mainly in aggressive and poorly differentiated types of BC. It should be noted that female BC survivors treated with anti-hormonal therapy showed lower levels of BBP than patients with BC. BPA and BPS were found in most samples from Mexico City. However, BPS was undetectable in women from Toluca City. DISCUSSION: The results of our study support the hypothesis of a positive association between exposure to phthalates and BC incidence.

Maternal perinatal exposure to bisphenol S induces an estrogenic like effect in glucose homeostasis in male offspring.

Bisphenol S (BPS) has been introduced into the industry as a safer alternative to bisphenol A (BPA). However, the recent studies have reported a possible association between BPS and disturbed glucose homeostasis, indicating that it may be a risk factor for type 1 and type 2 diabetes mellitus, obesity, and gestational diabetes mellitus. Nevertheless, the role of BPS in glucose metabolism remains controversial. In this study, we investigated the glucose metabolism of male Wistar rats born from dams that were BPS-exposed (groups: BPS-L (0.05 mg/kg/day), BPS-H (20 mg/kg/day)) during pregnancy and lactation. We observed that both BPS treated groups of animals presented a significant decrease in anogenital distance/weight1/3 , as compared to control animals, although no alterations in testosterone levels were observed. Furthermore, the BPS-L group presented a significant decrease in body weight from postnatal day (PND) 21 to adult stage. In addition, a significant increase in glucose tolerance, pancreatic ß-cell proliferation, the frequency of small islets, and the average ß-cell size at PND 36 was observed in this group. However, no changes in insulin serum levels and percentage of ß-cells were recorded. Furthermore, these changes were not preserved at the adult stage (PND 120). The results suggest that the administration of low doses of BPS during the perinatal period induced an estrogenic like effect, with males apparently becoming more female-like in their responses to a glucose challenge.

Critical review of the toxicity mechanisms of bisphenol F in zebrafish (Danio rerio): Knowledge gaps and future directions.

Replacement chemicals for bisphenol A, such as bisphenol F (BPF), are detected in aquatic environments worldwide and can potentially exert negative effects on aquatic organisms. We synthesized peer-reviewed literature reporting molecular and physiological responses in zebrafish following exposure to BPF, as BPF is closely related to BPA structure and is a dominant replacement chemical in the marketplace. Global concentrations of BPF in aquatic environments were compiled and compared to physiological and behavioral impacts reported in zebrafish (e.g., developmental abnormalities, oxidative stress, immunotoxicity, endocrine disruption, and neurotoxicity). Using computational approaches, we elucidate BPF-mediated molecular networks and reveal novel biomarkers associated with BPF exposure. Functional classes of proteins including inflammatory cytokines, ATPases, peroxidases, and aromatic l-amino decarboxylases represent novel, underexplored targets of toxicity. Most revealing of this critical review is that few studies report biological responses to BPF at levels present in aquatic environments. Recommendations for future investigations based on knowledge gaps include: (1) Mechanistic studies in the central nervous system of zebrafish to address neurotoxicity; (2) Behavioral assays in zebrafish that assess the effects of BPF on anxiolytic, social, and fear-related behaviors; (3) Studies that broaden understanding of potential endocrine disrupting effects of BPF, for example insulin signaling is predicted to be sensitive to BPF exposure; (4) Studies into metabolic disruption with a focus on glutathione and aromatic amino acids, based upon pathway analysis data; (5) Studies utilizing mixture exposures with other BPA analogs to reflect environmental conditions more accurately.

Environmental Pollution to Blame for Depressive Disorder?

Public concern has emerged about the effects of endocrine-disrupting compounds (EDCs) on neuropsychiatric disorders. Preclinical evidence suggests that exposure to EDCs is associated with the development of major depressive disorder (MDD) and could result in neural degeneration. The interaction of EDCs with hormonal receptors is the best-described mechanism of their biological activity. However, the dysregulation of the hypothalamic-pituitary-gonadal adrenal axis has been reported and linked to neurological disorders. At a worldwide level and in Mexico, the incidence of MDD has recently been increasing. Of note, in Mexico, there are no clinical associations on blood levels of EDCs and the incidence of the MDD. Methodology: Thus, we quantified for the first time the serum levels of parent compounds of two bisphenols and four phthalates in patients with MDD. The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP), and di-ethyl-phthalate (DEP), bisphenol A (BPA), and bisphenol S (BPS) in men and women with or without MDD were determined with a gas chromatograph-mass spectrometer. Results/conclusion: We found significant differences between concentrations of BBP between controls and patients with MDD. Interestingly, the serum levels of this compound have a dysmorphic behavior, being much higher in women (~500 ng/mL) than in men (≤10 ng/mL). We did not observe significant changes in the serum concentrations of the other phthalates or bisphenols tested, neither when comparing healthy and sick subjects nor when they were compared by gender. The results point out that BBP has a critical impact on the etiology of MDD disorder in Mexican patients, specifically in women.

Effects of bisphenols on Blood-Testis Barrier protein expression in vitro: A systematic review and meta-analysis.

Bisphenols are a group of environmental endocrine-disrupting chemicals that produce alterations in the expression of intercellular junction proteins of the Blood-Testis Barrier (BTB) involved in spermatogenesis. The association between bisphenol exposure and BTB protein expression is controversial. Therefore, we performed this systematic review and meta-analysis to clarify bisphenol effects on Sertoli cell BTB protein expression in vitro. The Standardized Mean Difference (SMD) with a 95 % confidence interval (95 % CI) was used to evaluate the association between alterations in the BTB protein expression and bisphenol exposure in vitro. Six articles were included in the meta-analysis. Bisphenol-A (BPA) exposure at 200 µM was associated with significant decrease in BTB protein expression (SMD = -2.70, 95 %CI: -3.59, -1.80, p het = 0.46, p = <0.00001). In the moderate (40-50 µM) and low dose (<25 µM), no significant associations were obtained. We also found a non-monotonic dose-response curve of bisphenol effect in ZO-1 protein expression; low and high doses presented a significant decrease compared to control, while moderate dose presented no change. The current temporary Tolerable Daily Intake (tTDI) of BPA is 4 µg/kg bw/day. The 5-25 µM doses of BPA are equivalent to ∼1-5 mg/kg bw, respectively. Although the low dose group (<25 µM) assessed doses below the previous NOAEL value, these doses are above the current tTDI. Thus, it is necessary to conduct more studies with lower bisphenol concentrations to avoid underestimating the potential adverse effects of bisphenols at doses below tTDI.

Fish pollutants MeHg and Aroclor cause permanent structural damage in male gonads and kidneys after prepubertal exposure.

This study investigated whether or not prepubertal exposure to the fish contaminants methylmercury (MeHg) and the polychlorinated bisphenol Aroclor in low doses interferes with the histomorphometry of the testes, epididymis, liver and kidneys in rats. Wistar male rats, 21 days old, were allocated into the following: control (n = 17, received corn oil), MeHg (n = 17, received MeHg at 0.5 mg/kg/day), Aroclor (n = 17, received Aroclor at 1.0 mg/kg/day), low mix (n = 18, received MeHg at 0.05 mg/kg/day and Aroclor at 0.1 mg/kg/day), high mix (n = 18, received MeHg at 0.5 mg/kg/day and Aroclor at 1.0 mg/kg/day). Dosing continued from post natal day (PND) 23 to 53, by gavage. Euthanasia was performed on PND 53; or, after an interval of 62 days without exposure to chemicals, on PND 115. The degree of maturation of the seminiferous epithelium was delayed in chemical-exposed groups and testicular interstitial oedema was observed at adulthood. The pattern of male gonad organization was changed in the Aroclor group on PND 53 and in all treated groups at adulthood. The animals from Aroclor, low mix and high mix groups showed a reduction in the number of Sertoli cells. Histological evidence of renal injury was observed in all chemical-exposed groups in both ages. A probable target for MeHg and Aroclor in the reproductive system was Sertoli cells, in which possible dysfunctions could be linked to the other testicular alterations. Curiously, the main deleterious effects were late outcomes, along with the absence of synergistic interaction of MeHg and Aroclor in the parameters investigated. In conclusion, fish pollutants MeHg and Aroclor caused permanent structural damage in male gonads and kidneys after prepubertal exposure, without showing clear chemical interactions.