Research Progress of the Endocrine-Disrupting Effects of Disinfection Byproducts.
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ABSTRACT:
SUBMITTER: Sui S
PROVIDER: S-EPMC9326600 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Assessing long-term health effects from a potentially harmful environment is challenging. Endocrine-disrupting compounds (EDCs) have become omnipresent in our environment. Individuals may or may not experience clinical health issues from being exposed to the increasing environmental pollution in daily life, but an issue of high concern is that also the non-exposed progeny may encounter consequences of these ancestral exposures. Progress in understanding epigenetic mechanisms opens new perspectives to estimate the risk of man-made EDCs. However, the field of epigenetic toxicology is new and its application in public health or in the understanding of disease etiology is almost non-existent, especially if it concerns future generations. In this review, we investigate the literature on transgenerational inheritance of diseases, published in the past 10 years. We question whether persistent epigenetic changes occur in the male germ line after exposure to synthesized EDCs. Our systematic search led to an inclusion of 43 articles, exploring the effects of commonly used synthetic EDCs, such as plasticizers (phthalates and bisphenol A), pesticides (dichlorodiphenyltrichloroethane, atrazine, vinclozin, methoxychlor), dioxins, and polycyclic aromatic hydrocarbons (PAHs, such as benzo(a)pyrene). Most studies found transgenerational epigenetic effects, often linked to puberty- or adult-onset diseases, such as testicular or prostate abnormalities, metabolic disorders, behavioral anomalies, and tumor development. The affected epigenetic mechanisms included changes in DNA methylation patterns, transcriptome, and expression of DNA methyltransferases. Studies involved experiments in animal models and none were based on human data. In the future, human studies are needed to confirm animal findings. If not transgenerational, at least intergenerational human studies and studies on EDC-induced epigenetic effects on germ cells could help to understand early processes of inheritance. Next, toxicity tests of new chemicals need a more comprehensive approach before they are introduced on the market. We further point to the relevance of epigenetic toxicity tests in regard to public health of the current population but also of future generations. Finally, this review sheds a light on how the interplay of genetics and epigenetics may explain the current knowledge gap on transgenerational inheritance.
| S-EPMC7218615 | biostudies-literature
Project description:Several hundred disinfection byproducts (DBPs) in drinking water have been identified, and are known to have potentially adverse health effects. There are toxicological data gaps for most DBPs, and the predictive method may provide an effective way to address this. The development of an in-silico model of toxicology endpoints of DBPs is rarely studied. The main aim of the present study is to develop predictive quantitative structure-activity relationship (QSAR) models for the reactive toxicities of 50 DBPs in the five bioassays of X-Microtox, GSH+, GSH-, DNA+ and DNA-. All-subset regression was used to select the optimal descriptors, and multiple linear-regression models were built. The developed QSAR models for five endpoints satisfied the internal and external validation criteria: coefficient of determination (R²) > 0.7, explained variance in leave-one-out prediction (Q²LOO) and in leave-many-out prediction (Q²LMO) > 0.6, variance explained in external prediction (Q²F1, Q²F2, and Q²F3) > 0.7, and concordance correlation coefficient (CCC) > 0.85. The application domains and the meaning of the selective descriptors for the QSAR models were discussed. The obtained QSAR models can be used in predicting the toxicities of the 50 DBPs.
| S-EPMC6151816 | biostudies-literature
Project description:Intensified use of disinfectants to control COVID-19 could unintentionally increase the disinfection byproducts (DBPs) in the environment. In indoor spaces, it is critical to determine the optimal disinfection practice to prevent the spread of the virus while keeping DBPs at relatively low levels in the air. The formation of DBPs exceed 0.1 μg/mg while hypochlorite dosed at >10 mg/m3. The total DBP concentrations in highly disinfected places (100-200 mg/m3 hypochlorite) were as high as 66.8 μg/m3, and the Hazard Index (HI) was up to 0.84, and both values were much higher than those in less disinfected places (<10 mg/m3 hypochlorite). Taking into account the HI, formation yields and the origin of the DBPs, we recommended 10 mg/m3 as the suggested hypochlorite dose to minimize DBPs generation during routine disinfection for controlling the coronavirus. DBPs in indoor air could be eliminated by ventilation, reducing the usage of personal care products, and wiping the solid surface with water before or after disinfection. These results highlighted the necessity to control air-borne DBPs and their associated health risks arising from intensified disinfection, and will guide the further development of evidence-based regulation on DBP exposure during disinfection and improve public health protection.
| S-EPMC8158349 | biostudies-literature
Project description:Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P), estradiol (E2), testosterone (T), human chorionic gonadotropin (hCG) and prolactin (PRL) were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1), estrogen sulfotransferase 1E1 (SULT1E1), steroid 5?-reductase 1 (SRD5A1) and steroid 5?-reductase 2 (SRD5A2). Furthermore, the transcriptional expression levels of progesterone receptor (PR), estrogen receptor (ER?) and androgen receptor (AR) were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth.
| S-EPMC4858197 | biostudies-literature
Project description:The introduction of drinking water disinfection greatly reduced waterborne diseases. However, the reaction between disinfectants and natural organic matter in the source water leads to an unintended consequence, the formation of drinking water disinfection byproducts (DBPs). The haloacetaldehydes (HALs) are the third largest group by weight of identified DBPs in drinking water. The primary objective of this study was to analyze the occurrence and comparative toxicity of the emerging HAL DBPs. A new HAL DBP, iodoacetaldehyde (IAL) was identified. This study provided the first systematic, quantitative comparison of HAL toxicity in Chinese hamster ovary cells. The rank order of HAL cytotoxicity is tribromoacetaldehyde (TBAL) ? chloroacetaldehyde (CAL) > dibromoacetaldehyde (DBAL) ? bromochloroacetaldehyde (BCAL) ? dibromochloroacetaldehyde (DBCAL) > IAL > bromoacetaldehyde (BAL) ? bromodichloroacetaldehyde (BDCAL) > dichloroacetaldehyde (DCAL) > trichloroacetaldehyde (TCAL). The HALs were highly cytotoxic compared to other DBP chemical classes. The rank order of HAL genotoxicity is DBAL > CAL ? DBCAL > TBAL ? BAL > BDCAL>BCAL ? DCAL>IAL. TCAL was not genotoxic. Because of their toxicity and abundance, further research is needed to investigate their mode of action to protect the public health and the environment.
| S-EPMC4791037 | biostudies-literature
Project description:Halobenzoquinones (HBQs) are a new class of drinking water disinfection byproducts (DBPs) and are capable of producing reactive oxygen species and causing oxidative damage to proteins and DNA in T24 human bladder carcinoma cells. However, the exact mechanism of the cytotoxicity of HBQs is unknown. Here, we investigated the role of glutathione (GSH) and GSH-related enzymes including glutathione S-transferase (GST) and glutathione peroxidase (GPx) in defense against HBQ-induced cytotoxicity in T24 cells. The HBQs are 2,6-dichloro-1,4-benzoquinone (DCBQ), 2,6-dichloro-3-methyl-1,4-benzoquinone (DCMBQ), 2,3,6-trichloro-1,4-benzoquinone (TriCBQ), and 2,6-dibromobenzoquinone (DBBQ). We found that depletion of cellular GSH could sensitize cells to HBQs and extracellular GSH supplementation could attenuate HBQ-induced cytotoxicity. HBQs caused significant cellular GSH depletion and increased cellular GST activities in a concentration-dependent manner. Our mass spectrometry study confirms that HBQs can conjugate with GSH, explaining in part the mechanism of GSH depletion by HBQs. The effects of HBQs on GPx activity are compound dependent; DCMBQ and DBBQ decrease cellular GPx activities, whereas DCBQ and TriCBQ have no significant effects. Pearson correlation analysis shows that the cellular GSH level is inversely correlated with ROS production and cellular GST activity in HBQ-treated cells. These results support a GSH and GSH-related enzyme-mediated detoxification mechanism of HBQs in T24 cells.
| S-EPMC4833019 | biostudies-literature
Project description:Flushing toilet with seawater is an effective method for preserving freshwater resources, but it introduces iodide and bromide ions into domestic wastewater. During chlorine disinfection, iodide and bromide ions in the saline wastewater effluent lead to the formation of iodinated and brominated aromatic disinfection byproducts (DBPs). Examples of aromatic DBPs include iodophenolic, bromophenolic and chlorophenolic compounds, which generally display substantially higher toxicity than haloaliphatic DBPs. This paper presented for the first time the rates of phototransformation of 21 newly identified halophenolic DBPs in seawater, the receiving waterbody of the wastewater effluent. The phototransformation rate constants (k) were in the range from 7.75 × 10-4 to 4.62 × 10-1 h-1, which gave half-lives of 1.5-895 h. A quantitative structure-activity relationship was established for the phototransformation of halophenolic DBPs as logk=-0.0100×ΔGf0+5.7528×logMW+0.3686×pKa-19.1607, where ΔGf0 is standard Gibbs formation energy, MW is molecular weight, and pKa is dissociation constant. This model well predicted the k values of halophenolic DBPs. Among the tested DBPs, 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol were found to exhibit relatively high risks on marine organisms, based on toxicity indices and half-lives. In seawater, the two DBPs underwent photonucleophilic substitutions by bromide, chloride and hydroxide ions, resulting in the conversion to their bromophenolic and chlorophenolic counterparts (which are less toxic than the parent iodophenolic DBPs) and to their hydroxyphenolic counterparts (iodo(hydro)quinones, which are more toxic than the parent iodophenolic DBPs). The formed iodo(hydro)quinones further transformed to hydroxyl-iodo(hydro)quinones, which have lower toxicity than the parent compounds.
| S-EPMC6390291 | biostudies-literature
Project description:The link between in utero and neonatal exposure to environmental toxicants, such as endocrine-disrupting chemicals (EDCs) and adult female reproductive disorders is well established in both epidemiological and animal studies. Recent studies examining the epigenetic mechanisms involved in mediating the effects of EDCs on female reproduction are gathering momentum. In this review, we describe the developmental processes that are susceptible to EDC exposures in female reproductive system, with a special emphasis on the ovary. We discuss studies with select EDCs that have been shown to have physiological and correlated epigenetic effects in the ovary, neuroendocrine system, and uterus. Importantly, EDCs that can directly target the ovary can alter epigenetic mechanisms in the oocyte, leading to transgenerational epigenetic effects. The potential mechanisms involved in such effects are also discussed.
| S-EPMC3009556 | biostudies-other
Project description:Background and objectiveHormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) is the most prevalent subtype of all BCs. The primary treatment modality is endocrine therapy (ET). Traditional adjuvant ET for early-stage breast cancer (EBC) has undergone extensive exploration and is relatively well-established. However, patients at high risk of recurrence may still experience early relapse, necessitating consideration of intensified adjuvant ET to reduce recurrence risk. The objective of this narrative review is to examine various strategies for intensifying adjuvant ET in EBC, thoroughly analyze key clinical studies, and summarize the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation.MethodsAs of March 2024, a comprehensive literature search, compilation, and analysis were conducted across PubMed, Baidu Scholar, ClinicalTrials.gov, and relevant academic conferences.Key content and findingsThere are numerous methods to intensify adjuvant ET: (I) combining ovarian function suppression (OFS) to reduce estrogen levels in the body and induce a state of artificial menopause to enhance the efficacy of ET; (II) individual extension of the duration of ET based on patients' varying risks of recurrence, with high-risk patients covering two peak recurrence periods; (III) the addition of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) can significantly extend invasive disease-free survival and reduce the risk of recurrence, serving as the main intensive treatment for high-risk patients; (IV) combination with bone-modifying drugs (BMD) can significantly reduce rates of bone metastasis and slightly enhance prognosis but is not commonly used in adjuvant settings; (V) combined with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, current studies only show a trend towards benefit in HR+ patients with germline BRCA1/2 mutations; more data are still needed to support its clinical benefit. This narrative review examines various strategies for intensifying adjuvant ET in EBC, critically evaluates key clinical studies, and summarizes the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation.ConclusionsIn the context where traditional adjuvant ET is relatively well-established, the emergence of novel ET has notably addressed issues of endocrine resistance more effectively. Various intensified adjuvant ET has shown potential in further reducing recurrence risk among high-risk patients. However, additional research and time are essential to determine the optimal approaches for intensified adjuvant ET.
| S-EPMC11341998 | biostudies-literature
Project description:The extent of our knowledge on the number of chemical compounds related to anthropogenic activities that can cause damage to the environment and to organisms is increasing. Endocrine disrupting chemicals (EDCs) are one group of potentially hazardous substances that include natural and synthetic chemicals and have the ability to mimic endogenous hormones, interfering with their biosynthesis, metabolism, and normal functions. Adverse effects associated with EDC exposure have been documented in aquatic biota and there is widespread interest in the characterization and understanding of their modes of action. Fish are considered one of the primary risk organisms for EDCs. Zebrafish (Danio rerio) are increasingly used as an animal model to study the effects of endocrine disruptors, due to their advantages compared to other model organisms. One approach to assess the toxicity of a compound is to identify those patterns of gene expression found in a tissue or organ exposed to particular classes of chemicals, through new technologies in genomics (toxicogenomics), such as microarrays or whole-genome sequencing. Application of these technologies permit the quantitative analysis of thousands of gene expression changes simultaneously in a single experiment and offer the opportunity to use transcript profiling as a tool to predict toxic outcomes of exposure to particular compounds. The application of toxicogenomic tools for identification of chemicals with endocrine disrupting capacity using the zebrafish model system is reviewed.
| S-EPMC5282603 | biostudies-literature