scholarly journals Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Di Nisio ◽  
Maria Santa Rocca ◽  
Luca De Toni ◽  
Iva Sabovic ◽  
Diego Guidolin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endocrine Disruption ◽  
Bone Development ◽  
Epidemiological Studies ◽  
Consumer Products ◽  
Target Cells ◽  
Surface Plasmon Resonance Analysis ◽  
Cellular Targets ◽  
Toxicological Studies

Abstract Perfluoroalkyl substances (PFAS) are a class of compounds used in industry and consumer products. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity, and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissues and cause altered bone development. Epidemiological studies have reported an inverse relationship between PFAS and bone health, however the associated mechanisms are still unexplored. Here, we present computational, in silico and in vitro evidence supporting the interference of PFOA on vitamin D (VD). First, PFOA competes with calcitriol on the same binding site of the VD receptor, leading to an alteration of the structural flexibility and a 10% reduction by surface plasmon resonance analysis. Second, this interference leads to an altered response of VD-responsive genes in two cellular targets of this hormone, osteoblasts and epithelial cells of the colorectal tract. Third, mineralization in human osteoblasts is reduced upon coincubation of PFOA with VD. Finally, in a small cohort of young healthy men, PTH levels were higher in the exposed group, but VD levels were comparable. Altogether these results provide the first evidence of endocrine disruption by PFOA on VD pathway by competition on its receptor and subsequent inhibition of VD-responsive genes in target cells.

scholarly journals Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Stephen J. Genuis ◽  
Sanjay Beesoon ◽  
Rebecca A. Lobo ◽  
Detlef Birkholz
Keyword(s):  
High Performance ◽  
Effective Means ◽  
Epidemiological Studies ◽  
Consumer Products ◽  
High Exposure ◽  
Estrogenic Effects ◽  
Toxicological Studies ◽  
Liquid Chromatography Tandem Mass ◽  
Ethylhexyl Phthalate

Background. Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion.Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry.Results. Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels.Conclusions. Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body.

Risk assessment of dietary exposure to methylmercury in fish in the UK

2007 ◽  
Vol 26 (3) ◽  
pp. 185-190 ◽  
Author(s):  
B J Maycock ◽  
D J Benford
Keyword(s):  
Risk Assessment ◽  
Dietary Exposure ◽  
Epidemiological Studies ◽  
Consumer Products ◽  
Laboratory Animals ◽  
Human Data ◽  
Toxicological Studies ◽  
Assessment Approach ◽  
Nutritional Data ◽  
The Uk

Risk assessment of chemicals in food is generally based upon the results of toxicological studies in laboratory animals, allowing for uncertainties relating to interspecies differences, human variability, and gaps in the database. Use of quantitative human data is preferable if available, as in the example of methylmercury. Methylmercury is a neurotoxic environmental contaminant, for which fish is the main source of dietary exposure. Human data from poisoning incidents and epidemiological studies have been used by expert committees to derive a guideline intake level for methylmercury, based on the susceptibility of the most sensitive lifestage, the developing fetus. In the UK, an expert group of nutritionists and toxicologists was formed to review the benefits and risks associated with fish consumption. A formal risk–benefit analysis was not possible because the nutritional data were not sufficiently quantitative. The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), therefore, modified the risk assessment approach to derive different guideline intake levels for different subgroups of the population. The COT opinion was used to provide targeted advice on how much fish can be consumed without undue risk from the contaminants. Consumption by adults of one weekly portion (140 g) of shark, swordfish or marlin, would lead to an exceedance of the guideline intake for methylmercury of 40–90%, set to protect the developing fetus, without considering intake from the rest of the diet. Pregnant women and women who may become pregnant within 1 year were, therefore, advised to avoid consumption of these species. Intakes in other adults would be within a higher guideline intake, set to protect groups of the population other than the developing fetus. However, consumption by children of one weekly portion of these species could lead to an exceedance of this guideline intake by up to 60%, without considering intake from the rest of the diet. It was, therefore, advised that consumption of these species by children should be avoided.

scholarly journals Vitamin D, adipose tissue, and obesity

2013 ◽  
Vol 15 (3) ◽  
Author(s):  
Julie Marcotorchino ◽  
Franck Tourniaire ◽  
Jean-François Landrier
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin D ◽  
Adipose Tissue ◽  
Cardiovascular Diseases ◽  
Vitamin D Deficiency ◽  
Epidemiological Studies ◽  
The Relationship ◽  
Diabetes And Obesity

AbstractEpidemiological studies have shown a link between vitamin D deficiency and numerous pathologies such as cancers, immunity diseases, cardiovascular diseases, hypertension, type 2 diabetes, and obesity. Recent studies in vitro and in animal models demonstrated an impact of vitamin D on adipose tissue and adipocyte biology. Such observations are of particular interest and provide mechanistic explanations on the relationship between vitamin D deficiency and obesity.

scholarly journals Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti–HIV-1 IgG without induction of maturation

Blood ◽  
2006 ◽  
Vol 107 (11) ◽  
pp. 4466-4474 ◽  
Author(s):  
Vincent Holl ◽  
Maryse Peressin ◽  
Sylvie Schmidt ◽  
Thomas Decoville ◽  
Susan Zolla-Pazner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inhibitory Activity ◽  
Hiv Transmission ◽  
Autologous Blood ◽  
Target Cells ◽  
Hiv Replication ◽  
Cellular Targets ◽  
Immature Dendritic Cells ◽  
Hiv 1

AbstractDuring mucosal HIV transmission, immature dendritic cells (DCs) present in the mucosa are among the first cellular targets of the virus. Previous studies have analyzed the inhibition of HIV-1 transfer from human mature DCs to T lymphocytes by neutralizing IgG, but so far no in vitro data regarding the capacity of antibodies to inhibit HIV-1 infection of immature DCs have been reported. Here, we found an increased HIV-inhibitory activity of monoclonal IgG and purified polyclonal IgG when immature monocyte-derived dendritic cells (iMDDCs) were used as target cells instead of autologous blood lymphocytes. We showed that FcγRII is involved in the mechanism for inhibiting HIV-1 infection of iMDDCs by IgG, whereas no induction of maturation was detected at concentrations of IgG that result in a 90% reduction of HIV replication. After induction of FcγRI expression on iMDDCs by IFN-γ, an augmentation of the HIV-inhibitory activity of IgG, related to the expression of FcγRI, was observed. Taken together, our results demonstrate the participation of FcγRs in HIV-1 inhibition by IgG when iMDDCs are the targets. We propose that IgG is able to efficiently inhibit HIV-1 replication in iMDDCs and should be one of the components to be induced by vaccination.

scholarly journals Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

2020 ◽  
Vol 17 (8) ◽  
pp. 2654 ◽  
Author(s):  
Francesca Gorini ◽  
Elisa Bustaffa ◽  
Alessio Coi ◽  
Giorgio Iervasi ◽  
Fabrizio Bianchi
Keyword(s):  
Thyroid Dysfunction ◽  
Direct Action ◽  
Epidemiological Studies ◽  
In Vivo Studies ◽  
Original Research ◽  
Long Term Effects ◽  
Toxicological Studies

Bisphenols (BPs), and especially bisphenol A (BPA), are known endocrine disruptors (EDCs), capable of interfering with estrogen and androgen activities, as well as being suspected of other health outcomes. Given the crucial role of thyroid hormones and the increasing incidence of thyroid carcinoma in the last few decades, this review analyzes the effects of BPS on the thyroid, considering original research in vitro, in vivo, and in humans published from January 2000 to October 2019. Both in vitro and in vivo studies reported the ability of BPs to disrupt thyroid function through multiple mechanisms. The antagonism with thyroid receptors (TRs), which affects TR-mediated transcriptional activity, the direct action of BPs on gene expression at the thyroid and the pituitary level, the competitive binding with thyroid transport proteins, and the induction of toxicity in several cell lines are likely the main mechanisms leading to thyroid dysfunction. In humans, results are more contradictory, though some evidence suggests the potential of BPs in increasing the risk of thyroid nodules. A standardized methodology in toxicological studies and prospective epidemiological studies with individual exposure assessments are warranted to evaluate the pathophysiology resulting in the damage and to establish the temporal relationship between markers of exposure and long-term effects.

scholarly journals Vitamin D in follicular development and oocyte maturation

Reproduction ◽  
2021 ◽  
Author(s):  
Fuhua Xu ◽  
Shally Wolf ◽  
O'ryai Green ◽  
Jing Xu
Keyword(s):  
Vitamin D ◽  
Animal Models ◽  
Oocyte Maturation ◽  
Molecular Mechanisms ◽  
Light Exposure ◽  
Follicular Development ◽  
Target Cells ◽  
Wide Range ◽  
The Impact

Vitamin D (VD) is a secosteroid hormone synthesized predominantly in the skin upon ultraviolet light exposure, which can also be obtained from dietary sources. In target cells, the bioactive VD binds to specific VD receptor to regulate downstream transcription of genes that are involved in a wide range of cellular processes. There is increasing recognition that the proper physiological levels of VD are critical for optimizing reproductive potential in women. The direct VD action in the ovary was first suggested in the 1980s. Since then, research has attempted to determine the role of VD in follicular development and oocyte maturation in animal models and clinical settings. However, data published to date are inconclusive due to the complexity in VD metabolism and the fact that VD actions are pervasive in regulating physiological functions in various systems, including the reproductive, endocrine and nervous systems that control reproduction. This review summaries in vitro, in vivo, and clinical evidence regarding VD metabolism and signaling in the ovary, as well as VD-regulated or VD-associated ovarian follicular development, steroidogenic function, and oocyte maturation. It is suggested that adequate animal models are needed for well-controlled studies to unravel molecular mechanisms of VD action in the ovary. For clinical studies, follicular development and function may be evaluated more effectively in a relatively homogeneous patient population under a well-controlled experimental design. A comprehensive understanding of VD-regulated folliculogenesis and oogenesis will provide critical insight into the impact of VD in female reproductive health.

scholarly journals Endocrine Disruption by Mixtures in Topical Consumer Products

Cosmetics ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 61 ◽  
Author(s):  
Emiliano Ripamonti ◽  
Elena Allifranchini ◽  
Stefano Todeschi ◽  
Elena Bocchietto
Keyword(s):  
Endocrine Disruptors ◽  
Endocrine Disruption ◽  
Hormone Receptors ◽  
Health And Safety ◽  
Test Methods ◽  
Potential Interaction ◽  
Consumer Products ◽  
Cumulative Effects ◽  
Active Substances

Endocrine disruption has been gathering increasing attention in the past 25 years as a possible new threat for health and safety. Exposure to endocrine disruptor has been progressively linked with a growing number of increasing disease in the human population. The mechanics through which endocrine disruptors act are not yet completely clear, however a number of pathways have been identified. A key concern is the cumulative and synergic effects that endocrine disruptors could have when mixed in consumer products. We reviewed the available literature to identify known or potential endocrine disruptors, as well as endocrine active substances that could contribute to cumulative effects, in topical consumer products. The number of endocrine actives used daily in consumer products is staggering and even though most if not all are used in concentrations that are considered to be safe, we believe that the possibility of combined effects in mixtures and non-monotonic dose/response is enough to require further precautions. A combined in vitro approach based on existing, validated OECD test methods is suggested to screen consumer products and mixtures for potential interaction with estrogen and androgen hormone receptors, in order to identify products that could have cumulative effects or support their safety concerning direct endocrine disruption capabilities.

Medium and long-chain structured triacylglycerol enhance Vitamin D bioavailability in emulsion-based delivery system: a combination of in vitro and in vivo studies

2022 ◽  
Author(s):  
Yiwen Guo ◽  
Ying Xu ◽  
Tao Zhang ◽  
Yandan Wang ◽  
Ruijie Liu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Delivery System ◽  
Calcium Homeostasis ◽  
Epidemiological Studies ◽  
In Vivo Studies ◽  
System A ◽  
Structured Triacylglycerol ◽  
Long Chain

Vitamin D (VitD) is an essential fat-soluble micronutrient required for maintaining and regulating calcium homeostasis. Although sunlight can provide VitD, epidemiological studies indicate that VitD deficiency and insufficiency are widespread....

Toxicological Studies of a Representative Xerox Reprographic Toner

1999 ◽  
Vol 18 (1) ◽  
pp. 23-34 ◽  
Author(s):  
George H. Y. Lin ◽  
Joseph C. Wilson
Keyword(s):  
Safety Concern ◽  
Safety Issue ◽  
Chinese Hamster ◽  
Health And Safety ◽  
Consumer Products ◽  
Worst Case ◽  
Inhalation Study ◽  
Charge Control ◽  
Toxicological Studies

Typical Xerox reprographic toners consist of a thermoplastic polymer as the major component, a colorant (carbon black or color pigment), and low quantities of additives such as charge control and/or lubricating agents. Another type of Xerox toner contains iron oxides and a polymer as the major components. Among all toners marketed by Xerox Corporation, the original 1075 toner (being discontinued and reformulated) was a major safety concern, because it contained approximately 2% cetylpyridinium chloride (CPC) as a charge control agent. CPC by itself is very toxic and causes severe irritation to the eye and skin. Although CPC has been used in very low concentrations in consumer products such as mouthwash, it was unknown whether a 50-fold dilution of CPC in the toner formulation would represent any safety issue. Therefore, a series of toxicological testing on the original 1075 toner was conducted. The test results indicate that the original Xerox 1075 toner was practically nontoxic following acute oral, dermal, and inhalation exposures; nonirritating to the eye; nonir-ritating/nonsensitizing to the skin; nonmutagenic in a battery of short-term assays (Ames Salmnonella/microsome assay, mouse lym-phoma assay, in vitro sister chromatid exchange assay in Chinese hamster ovarian cells, and in vitro BALB/3T3 cell transformation assay); and nonteratogenic in rats when inhaling the toner dust up to 1.2 g/m3. In addition, no mutagenic responses were observed from testing the urine or feces (by Ames test) and bone marrow (by examining micronucleus formation) of rats exposed to the toner dust at 1.3 g/m3 at the end of a subchronic inhalation study. Because all Xerox toners are alike, the toxicology of the original Xerox 1075 toner was considered a “worst-case” situation, relative to health and safety. However, it did not appear to represent any health and safety issue. The results of this study, together with the fact that no evidence of carcinogenicity was found in the Xerox chronic inhalation study on toner, indicate that Xerox toners are not safety hazards, with respect to the end points indicated in this report.

scholarly journals Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 597 ◽  
Author(s):  
Daniele Vergara ◽  
William H. Catherino ◽  
Giuseppe Trojano ◽  
Andrea Tinelli
Keyword(s):  
Vitamin D ◽  
Biological Effects ◽  
Large Population ◽  
Uterine Fibroids ◽  
Epidemiological Studies ◽  
Vitamin D Supplementation ◽  
Ecm Remodeling ◽  
Beneficial Effects ◽  
Clinical Benefits

Uterine fibroids (UFs) are the most common benign gynecological tumors. It was estimated that fifty percent of women presenting with UFs has symptomatology that negatively influences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman’s desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial.

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