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Triclosan in Plasma and Milk from Swedish Nursing Mothers and Their Exposure via Personal Care Products
Abstract
The bactericide triclosan is commonly used in e.g. plastics, textiles and health care products. In vitro studies on rat and human biological systems indicate that triclosan might exert adverse effects in humans. Triclosan has previously been found in human plasma and milk, but neither the primary source of human exposure nor the efficiency of triclosan transfer to human milk is known. In this study, plasma and milk were sampled from 36 mothers and analyzed for triclosan. Scrutinization of the women's personal care products revealed that nine of the mothers used toothpaste, deodorant or soap containing triclosan. Triclosan and/or its metabolites were omnipresent in the analyzed plasma and milk. The concentrations were higher in both plasma and milk from the mothers who used personal care products containing triclosan than in the mothers who did not. This demonstrated that personal care products containing triclosan were the dominant, but not the only, source of systemic exposure to triclosan. The concentrations were significantly higher in plasma than in milk, indicating that infant exposure to triclosan via breast milk is much less than the dose in the mother.
... Any organochlorine, TCS-induced increase in pro-inflammatory responsiveness could result in chronic inflammation, which is associated with numerous pathologies, including cardiovascular disease and several types of cancers (Amin et al., 2020;Dinarello, 2009;Kaneko et al., 2019;Lewis et al., 2006;Shirazi et al., 2017;Singh et al., 2019;Voronov et al., 2003). Additionally, TCS was detected in 75% of 2517 human urine samples at concentrations of 2.4 -3790 μg/L (Calafat et al., 2008), in 61% of 90 urine samples from age 6 -8-year-old girls (Wolff et al., 2007) and in human blood, TCS was detected in the range between 4.1 -19 ng/g in blood serum samples (Allmyr et al., 2006(Allmyr et al., , 2008. TCS concentrations between 100 -2100 μg/kg of lipid were detected in 96.8% of 62 breast milk samples (Dayan, 2007), and concentrations of TCS in breast milk were detected between 0.018 to 0.95 ng/g (Allmyr et al., 2006). ...
... Additionally, TCS was detected in 75% of 2517 human urine samples at concentrations of 2.4 -3790 μg/L (Calafat et al., 2008), in 61% of 90 urine samples from age 6 -8-year-old girls (Wolff et al., 2007) and in human blood, TCS was detected in the range between 4.1 -19 ng/g in blood serum samples (Allmyr et al., 2006(Allmyr et al., , 2008. TCS concentrations between 100 -2100 μg/kg of lipid were detected in 96.8% of 62 breast milk samples (Dayan, 2007), and concentrations of TCS in breast milk were detected between 0.018 to 0.95 ng/g (Allmyr et al., 2006). Lastly, TCS has been found in indoor dust (~1.1 μg/g) (Canosa et al., 2007) and foods (0.02 -0.15 ng/g) such as dairy products, vegetables, meat, fish, and egg (Allmyr et al., 2006). ...
... TCS concentrations between 100 -2100 μg/kg of lipid were detected in 96.8% of 62 breast milk samples (Dayan, 2007), and concentrations of TCS in breast milk were detected between 0.018 to 0.95 ng/g (Allmyr et al., 2006). Lastly, TCS has been found in indoor dust (~1.1 μg/g) (Canosa et al., 2007) and foods (0.02 -0.15 ng/g) such as dairy products, vegetables, meat, fish, and egg (Allmyr et al., 2006). ...
... Triclosan (TCS) is an organochlorine compound incorporated as an antibacterial agent into medical and personal care products such as topical antiseptics, deodorants, toothpaste, anti-bacterial soaps, dishwashing liquids, acne treatments, makeup, and lotions added (Morrall et al. 2004; Thompson et al. 2005;Weatherly and Gosse 2017). TCS is readily absorbed through the skin and is found in breast milk, blood, and urine (Allmyr et al. 2006(Allmyr et al. , 2008Calafat et al. 2008;Yin et al. 2016). Studies have found approximately 1 μM TCS in human blood plasma upon ingestion of TCS-containing mouthwash ). ...
... Here we examine if TSC is simply increasing release of pre-existing stores of these cytokines or whether it has the potential to increase cellular production of these potent inflammatory proteins. This will be addressed by measuring effects of TCS, in the concentration range seen in human tissues (Allmyr et al. 2006;Calafat et al. 2008;Thompson et al. 2005; Weatherly and Gosse 2017), on both secretion and intracellular levels of these cytokines. The role of MAPKs in any TCS-induced increases in IL-1β and IL-6 production will be examined as will the effects of TCS exposures on the level of IL-1β and IL-6 mRNA. ...
Triclosan (TCS) is an antimicrobial compound widely used in personal hygiene products such as mouthwash and toothpaste; and has been found in human blood, breast milk, and urine. Interleukin (IL)-6 and IL-1 beta (IL-1β) are pro-inflammatory cytokines regulating cell growth, tissue repair, and immune function; increased levels of each have been associated with many diseases, including cancer. Previous studies showed that TCS at concentrations between 0.05 and 5 µM consistently increased the secretion of IL-1β and IL-6 from human immune cells within 24 h of exposure. The current study demonstrates that this increase in secretion was not due simply to release of existing stores but was due to an increase in cellular production/levels (both secreted and intracellular levels) of each of these cytokines. Production of IL-1β and IL-6 was increased by exposure to one or more concentration of TCS at each length of exposure (10 min, 30 min, 6 h, and 24 h). TCS-induced stimulation of cytokine production was shown to be dependent on the mitogen-activated protein kinase (MAPK) p44/42 (ERK 1/2). It was also shown that these TCS-induced increases in IL-1β and IL6 production were accompanied by increased mRNA for IL-1β and IL-6. The ability of TCS to increase production indicates that rather than activating a self-limiting process of depleting cells of already existing stores of IL-1β or IL-6, TCS can stimulate a process that has the capacity to provide sustained production of these cytokines and thus may lead to chronic inflammation and its pathological consequences.
... The observed decrease in urinary triclosan ran counter to our expectation that changes in cleaning habits and increased hand hygiene practices [7,21] might increase systemic exposure to triclosan. In 2016, the Food and Administration banned triclosan as an active ingredient in hand soap [35] and hand sanitizers [36], though dermal absorption may still occur due to its presence in other personal care products (e.g., antiperspirants) or disinfectants [37][38][39]. Data from NHANES suggest that urinary triclosan concentrations in the U.S. are decreasing overall [40], so this secular trend as triclosan is increasingly phased out of consumer products may be a stronger overall driver of urinary triclosan concentrations than potential behavior changes during the study time frame. ...
Previous research indicates that the COVID-19 pandemic catalyzed alterations in behaviors that may impact exposures to environmental endocrine-disrupting chemicals. This includes changes in the use of chemicals found in consumer products, food packaging, and exposure to air pollutants. Within the Environmental influences on Child Health Outcomes (ECHO) program, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether urinary concentrations of a wide range of potential endocrine-disrupting chemicals varied before and during the pandemic. Drawing from three racially, ethnically, and socioeconomically diverse ECHO cohorts, we assessed key differences in urinary chemical concentrations related to environmental exposures through food packaging, use of disinfectants, personal care products and air pollutants using repeated urine samples in a subset of 47 participants, who contributed a urine sample prior to the pandemic (between October 2018 and February 2020) and a subsequent urine sample after the pandemic began (between March 2020 and April 2021). We measured urinary concentrations of analytes across several chemical groups, including polycyclic aromatic hydrocarbons (PAHs), phthalates/alternative plasticizers, synthetic phenols (parabens, bisphenols, triclosan, benzophenones), organophosphate esters (OPEs), insecticides and fungicides. Multivariable linear mixed models accounting for key covariates and clustering within cohort and across repeated samples were used to estimate the change in urinary analyte concentrations across time points. We observed decreases in urinary concentrations of some PAHs, bisphenols, benzophenones, and triclosan, and increases in specific OPEs. These biomarker data mirror some of the behavior changes reported in our prior work and support the observation that the pandemic-related behavior changes lead to alterations in chemical exposures that have been linked to adverse health outcomes.
... Other important DESs are natural deep eutectic solvents (NADESs), which are obtained from natural precursors [10]. The green characteristic and versatility of DESs and NADESs have allowed their efficient use in organic substances extraction in environmental water samples [11,12], where is possible to find triclosan (5-chloro-2-(2,4-dichlorophenoxy) phenol), a compound used as an antiseptic agent in products such as soaps, toothpastes, skin creams, deodorants, and cosmetics [13][14][15]. Nevertheless, this compound is classified as a disruptive chemical for endocrine system [16,17]. ...
A rapid and effective analytical method was developed for the detection of triclosan in wastewater samples using a hydro-phobic deep eutectic solvent thymol-lidocaine (Thy-Lid, molar ratio of 1:1) and dispersive liquid-liquid microextraction (DLLME). The analyte was determined by high-performance liquid chromatography with a photodiode array detector (HPLC-PDA), obtaining a detection limit of 0.38 µg/L, a recovery rate of 99%, and an enrichment factor of the analyte in the water of 80. A factorial design was used to optimize the analytical signal to improve the time and reduce the cost of the method. Combining this chemometric optimization tool with a green solvent and DLLME allows for obtaining an analytical methodology aligned with the principles of green analytical chemistry, enabling the inexpensive, selective, and rapid analysis of triclosan in real wastewater.
... [39] The fragrance was either natural at its origin, or derived from organic materials, such as essential oils or natural extracts; or synthesized from a mixture of chemicals [40]; with adverse effects on health or the environment, including contact dermatitis (irritant and/or allergic), non-eczematous contact reactions, photosensitivity, photoallergy and immediate contact reactions, which can have a negative impact on quality of life [41][42][43] Triclosan is an antimicrobial additive considered potentially harmful to health as an endocrine disruptor, following prolonged use. Continuous exposure to very low or minimal concentrations of triclosan can lead living organisms to absorb this compound [44,45]. This is how triclosan was banned in 2013 by the FDA [46]. ...
Endocrine disruptors are exogenous substances that alter the functions of the endocrine system and therefore induce harmful effects on the health of an intact organism, its descendants, or populations. They are at the heart of current health concerns, associated with other additives such as dyes and perfumes that constitute a source of allergy in predisposed individuals. The objective of this study is to identify and give the danger of endocrine disruptors, allergens and dyes in common cosmetic products for infants. Our study is described as descriptive, cross-sectional with prospective collection, and included all childcare cosmetic products with a label providing information on the chemical composition and present on the Kolwezi market. In a total of 48 ranges of cosmetic products analyzed, we found 10 types of endocrine disruptors, 13 types of allergens and 6 classes of dyes. Parabens are the most present endocrine disruptors in baby cosmetic products, followed by fragrance; and powder, followed by soap, are the products that contain more endocrine disruptors. Limonene is the most present allergen followed by geraniol; And powder, soap followed by lotion are the products that contain the most. Tartrazine is the most present dye and especially in soaps and lotions. These exogenous substances cause harmful effects on human health, which are accentuated in the most fragile, such as infants.
... As a contaminant, TCS has been detected in surface and drinking waters, with which it can enter the human body [4,5]. This compound can also be absorbed through human skin and oral mucosa and is found in various human tissues and fluids, such as milk and blood of nursing mothers [6,7]. Moreover, TCS was detected in urine samples with concentrations ranging from 0.08 to 0.71 µM [8], which suggests its higher amount in the human body. ...
Triclosan (TCS) is a widely used antimicrobial, antifungal, and antiviral agent. To date, it has been reported that
TCS can enter the human body and disrupt hormonal homeostasis. Therefore, the aim of our paper was to
evaluate the impact of TCS on astrocytes, i.e. a crucial population of cells responsible for steroid hormone
production. Our data showed that, in mouse primary astrocyte cultures, TCS can act as an endocrine disrupting
chemical through destabilization of the production or secretion of progesterone (P4), testosterone (T), and
estradiol (E2). TCS affects the mRNA expression of enzymes involved in neurosteroidogenesis, such as Cyp17a1,
17β-Hsd, and Cyp19a1. Our data showed that a partial PPARγ agonist (honokiol) prevented changes in Cyp17a1
mRNA expression caused by TCS. Similarly, honokiol inhibited TCS-stimulated P4 release. However, rosiglitazone
(classic PPARγ agonist) or GW9662 (PPARγ antagonist) had a much stronger effect. Therefore, we believe
that the changes observed in the P4, T, and E2 levels are a result of dysregulation of the activity of the aforementioned
enzymes, whose expression can be affected by TCS through a Pparγ-dependent pathway. TCS was
found to decrease the aryl hydrocarbon receptor (AhR) and Sirtuin 3 protein levels, which may be the result of
the activation of the these proteins. Since our study showed dysregulation of the production or secretion of
neurosteroids in astrocytes, it can be concluded that TCS reaching the brain may contribute to the development
of neurodegenerative diseases in which an abnormal amount of neurosteroids is observed.
... However, the by-product called methyl triclosan is formed during wastewater treatment plant, having more persistence than TCS, which is stable, lipophilic, and resistant to photolysis (Balmer et al. 2004) and tendency to bioaccumulation in aquatic organisms (Buser et al. 2006). TCS also determined in the plasma of dolphins (Fair et al. 2009), urine of human being (Calafat et al. 2008), and more concentration of TCS detected in the human breast samples (Allmyr et al. 2006). Adhikari et al. (2022) reported that a significant reduction in the use of TCS and TCC was detected in Arizona wastewater collected after the 2017 FDA ban on antimicrobials and during the COVID-19 pandemic, however other antimicrobial compounds, such as parabens (MePb, EtPb, and PrPb), increased significantly in waste water during the local epidemic. ...
COVID-19, a novel coronavirus, sparked a worldwide pandemic in 2019. It has led a serious threat to human life and has
a signifcant negative impact on livelihoods and food security, either directly or indirectly. As of 26 July 2023, rolling data
indicate that 768,560,727 people have been infected with COVID-19, of which 6,952,522 deaths have been reported to the
World Health Organization. The aim of this review is to comprehensively assess the multifaceted impact of COVID-19 on
the aquatic environment, with a specifc focus on elucidating it’s implications for fsheries. A literature review examined
COVID-19’s impact on fsheries, exploring this emerging academic feld by meticulously searching terms in reputable journal
databases. The sudden increase in plastics and medical trash during the COVID-19 pandemic, on the other hand, disguised
the positive efects and continued to increase the risks of river pollution, particularly micro plastics, medical products, and
antiseptics. Drugs used during pandemics in ecological systems and their potential efects of COVID-19 on aquatic animals
and human health have been updated. This review documents the potential efects of COVID-19 on the fshery environment,
with a special focus on fsheries and aquaculture. It also highlights improvements in aquatic biodiversity resulting from movement restrictions, reduced illegal fshing, and the closure of industries. Besides, restoration strategies for revival of aquatic
biodiversity, ecosystem health, and sustainable fsheries food production through efective regulation and eco-resources have
been thoroughly discussed. In conclusion, the COVID-19 lockdown brought dual efects on the environment, yielding benefts such as reduced pollution and aquatic resource recovery but also detrimentally impacting small-scale fsheries, causing
job losses. The pandemic’s overall threat persists, particularly in developing nations, overshadowing positive impacts and
posing unprecedented global challenges.
... TCS causes increased sensitivity to allergies, characterizing it as an allergen [21,22]. TCS enters the human body through the skin and oral mucosa [23] and is detected in the blood and milk of nursing mothers and urine [24,25]. ...
Endocrine-disrupting chemicals (EDCs) are environmental pollutants. Since EDCs are present in various consumer products, contamination of human beings is very common. EDCs have deleterious effects on various systems of the body, especially the endocrine and reproductive systems. EDCs interfere with the synthesis, metabolism, binding, or cellular responses of natural estrogens and alter various pathways. Biological samples such as blood, saliva, milk, placental tissue, and hair are frequently used for biomonitoring and the detection of EDCs. Early detection and intervention may help in preventing congenital anomalies and birth defects. The common methods for determining the presence of EDCs in body fluids include gas chromatography, high-performance liquid chromatography, and mass spectrometry. Understanding the health effects and dangers of EDC is important, given their widespread use. This mini-review aims to summarize the adverse biological effects of several important classes of EDCs and highlights future perspectives for appropriate control.
... Structure, names, and properties of Triclosan. 5-Cloro-2-(2,4dichlorophenoxy) phenol C 12 H 7 Cl 3 O 2 289.54 g/mol (Adolfsson-Erici et al., 2002;Bhargava & Leonard, 1996;Perencevich et al., 2001;Witorsch, 2014). in the breast milk and blood of nursing mothers (Allmyr et al., 2006) and human urine (Calafat et al., 2008). TCS was detected in 75% of the US population by 2004, with urine concentrations ranging from 7.9 nM -13.1 μM (Calafat et al., 2008). ...
... Biomagnification through food chain as well as bioaccumulation results in higher amounts of TCS concentration in human body [15]. The concentration of TCS observed in different human fluids is presented in Table 2 [29][30][31][32][33][34][35][36][37]. ...
... Other EDCs Triclosan (TCS) is an antimicrobial agent widely used in consumer products and is an EDC with estrogenic and androgenic activity (175,176). Due to its widespread use, TCS has been detected in the environment, as well as in human urine, blood and milk samples (177)(178)(179). Although some in vivo data suggests that TCS is a developmental and reproductive toxicant (180)(181)(182)(183), it is not currently known whether long-term exposure during critical windows of development is associated with adverse neurobehavioral outcomes in humans. ...
Hormones are important regulators of key processes during fetal brain development. Thus, the developing brain is vulnerable to the action of chemicals that can interfere with endocrine signals. Epidemiological studies have pointed toward sexually dimorphic associations between neurodevelopmental outcomes, such as cognitive abilities, in children and prenatal exposure to endocrine disrupting chemicals (EDCs). This points toward disruption of sex steroid signalling in the development of neural structures underlying cognitive functions, such as the hippocampus, an essential mediator of learning and memory processes. Indeed, during development, the hippocampus is subjected to the organizational effects of estrogens and androgens, which influence hippocampal cell proliferation, differentiation, dendritic growth and synaptogenesis in the hippocampal fields of Cornu Ammonis and the dentate gyrus. These early organizational effects correlate with a sexual dimorphism in spatial cognition and are subject to exogenous chemical perturbations. This review summarises the current knowledge about the organizational effects of estrogens and androgens on the developing hippocampus and the evidence for hippocampal-dependent learning and memory perturbations induced by developmental exposure to EDCs. We conclude that, while it is clear that sex hormone signalling plays a significant role during hippocampal development, a complete picture at the molecular and cellular levels would be needed to establish causative links between the endocrine modes of action exerted by EDCs and the adverse outcomes these chemicals can induce at the organism level.
... En la leche materna también es posible encontrar TCS, de acuerdo a datos obtenidos de mujeres que usaban PTCS, así la C.C. de TCS encontrada fue de 0.018 to 0.95 ng/g, lo que representa una ingesta de 570 ng/día en un bebé de 4 kg ingiriendo 150 mL/kg/día de leche materna (30). Entonces un neonato puede estar expuestos a la absorción de TCS, lo que también obliga a preguntarse si existe un riesgo para el desarrollo del bebé debido a la ingesta del compuesto. ...
Triclosan is an antimicrobial drug that is widely used in products for human hygiene, beauty and home cleanliness. It is a common compound in toothpaste that have showed efficacy on the control and treatment of gingivitis. However, during the last decade, the triclosan has been extensively investigated because of its cytotoxicity, its ability to disturb cellular mechanisms on endocrine-system cells, and because of its cancerogenic in vitro and in vivo properties. Moreover, public opinion has paid attention to the toxic action of the triclosan. Thus, the dentist should know the state of the art about the detrimental effects of triclosan on patients’ health. This review explores the triclosan on its cytotoxicity, in vitro and in vivo cancerogenic effects, absorption in humans, and the toxic effects caused by triclosan toothpaste.
... Due to its widespread use, people are exposed to TCS through dermal mucosal absorption and ingestion [307,308]. Therefore, TCS has been detected in human urine, plasma, breast milk, brain, liver, and adipose tissue [309][310][311][312][313][314]. Furthermore, several studies have noted higher concentrations of TCS in females than males [315]. ...
Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder among women of reproductive age. The pathogenesis of PCOS remains elusive; however, there is evidence suggesting the potential contribution of genetic interactions or predispositions combined with environmental factors. Among these, endocrine disrupting chemicals (EDCs) have been proposed to potentially contribute to the etiology of PCOS. Granulosa and theca cells are known to cooperate to maintain ovarian function, and any disturbance can lead to endocrine disorders, such as PCOS. This article provides a review of the recent knowledge on PCOS pathophysiology, the role of granulosa and theca cells in PCOS pathogenesis, and the evidence linking exposure to EDCs with reproductive disorders such as PCOS.
... TCA causes endocrine disruption and has potential adverse effects in humans. It has been detected in human blood, breast milk, nails, and urine samples [2]. TCA stores itself in fatty tissues which make it difficult to get rid of upon accumulation. ...
Triclosan (TCA) is an antibacterial and antimicrobial compound that is incorporated into toothpaste, soap, and liquid dishwasher. Continuous TCA exposure may contribute to the emergence of antibiotic-resistant bacteria in the microbiome. Triclosan also reacts to form dioxins, which bioaccumulate and are toxic to aquatic organisms, impedes the thyroid hormone metabolism of the human body. Laccases are multi copper-containing enzymes that can degrade the aromatic compounds and thus reduce their toxicity. To effectively degrade the compound, it is essential to understand the molecular function of the enzyme. Hence, a molecular docking study of laccase enzymes with Triclosan was done. The Tramates versicolor laccase structure was retrieved from PDB and ligand structure was taken from Pubchem. The binding mode and interaction of TCA and laccase were studied using Auto dock Vina software and the stability of the docked complex had been explored via Molecular Dynamics (MD) simulation study using Schrodinger Desmonde. The binding affinity score was found to be −6.5kcal/mol. The majority of the residues in RMSF were within the 2.5Å limit. The radius of gyration remained within the range from 21.7 to 22.1Å for Laccase – TCA complex throughout the 50 ns simulation. MD simulation results show that the enzyme complex remains stable all through the catalytic action.
... Given its widespread usage, it is not surprising that the concentration of TCS in groundwater, as well as in soil, is continually rising due to its poor solubilization and effective accumulation, consequently posing a threat to human health and the environment. Although TCS is not considered as toxic as other organic pollutants, it might accumulate in the human body for periods, posing long-duration health risks [24]. Another major problem of TCS is that its degradation results in other harmful products such as methyl-triclosan, whose lipophilicity and resistance to biodegradation and photolysis make this metabolite even more dangerous to the environment than TCS [25]. ...
Nanoparticles of TiO2 are suitable for many catalytic and photocatalytic applications due to their extraordinary properties such as superhydrophobicity, semiconductivity, electron-rich, and environmental compatibility. The main crystalline phases of TiO2, anatase, and rutile possess different crystal structures, crystallinity, crystalline sizes, and specific surface areas, and these characteristics directly affect the catalytic performance of TiO2. In the present study, domestic carbon material enhanced with TiO2 nanoparticles was synthesized and used for the construction of a modified carbon paste electrode. The electrocatalytic activity of the modified electrodes was investigated depending on the TiO2 crystalline phases in the electrode material. Furthermore, the obtained working electrode was utilized for triclosan detection. Under optimized experimental conditions, the developed electrode showed a submicromolar triclosan detection limit of 0.07 µM and a wide linear range of 0.1 to 15 µM. The relative standard deviations for repeatability and reproducibility were lower than 4.1%, and with satisfactory selectivity, the proposed system was successfully applied to triclosan monitoring in groundwater. All these results confirm that the sustainable production of new and domestically prepared materials is of great benefit in the field of electrocatalysis and that the morphology of such produced materials is strongly related to their catalytic properties.
Triklosan [5-chloro-2-(2,4-dichlorophenoxy) phenol] ya da ticari ismiyle “Irgasan” geniş spektrumlu güçlü bir antimikrobiyal ajan olarak bilinmektedir. Amerika Birleşik Devletleri Çevre Koruma Ajansı (USEPA) tarafından “pestisit” olarak tescillenmiştir. Avrupa’da her yıl yaklaşık 450 ton triklosanın kullanıldığı tahmin edilmektedir. Triklosanın % 85’i kişisel bakım ürünlerinde, % 5’i tekstil endüstrisinde ve % 10’u da plastik ve gıda ile temas eden maddelerin üretiminde yaygın olarak kullanılmaktadır. Kapsamlı kullanımı nedeniyle, insanlarda ve çevrede triklosan birikimi tespit edilmiştir. Triklosan çevresel açıdan toksik bir madde olup, toksisitesi ile çalışmalar yürütülmekte ve farklı canlı gruplarında toksik etki mekanizması aydınlatılmaktadır. Bu makale, triklosan’ın çevresel akıbeti, insan ve diğer canlı gruplarında maruziyeti, anti-mikrobiyal aktivitenin etkinliği, toksisitesi ve çevresel arıtım mekanizmaları hakkındaki verileri gözden geçirmektedir.
The COVID-19 pandemic has had a significant impact on weekly commuting activities through the promotion of remote work, especially from home. This “new normal” has the potential to alleviate the congestion and transportation externalities associated with commuting. In the literature, optimal first-best road pricing has been identified as a complementary strategy for reducing traffic congestion. However, the relationship between optimal road charges and work-from-home (WFH) arrangements is typically considered only with respect to the direct environmental and time costs borne by road users. The indirect effects of WFH on other road users, such as reduced vehicular emissions, time lost in traffic, fuel consumption, and wear-and-tear costs per mile, are often overlooked. This study developed a simple analytical model to analyze the impact of WFH on optimal environmental road pricing, taking into consideration its positive effects on other road users. The results showed that the potential reduction in road charges associated with WFH arrangements was due not only to the direct time and environmental costs imposed on others while in traffic, but also to the corresponding decreases in environmental damage and wear-and-tear costs for other road users resulting from alleviated congestion and traffic density. This study demonstrated that WFH can serve as a policy tool to reduce road congestion and charges, benefiting not only individuals who choose to work remotely but also other road users at the same time. In addition, promoting WFH policies may improve environmental quality and reduce travel time for both remote workers and the wider community.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by excess androgen and infertility due to anovulatory failure. A significant fraction of the world's population is affected by the infertility condition known as PCOS. Due to the disease's complicated nature and overlapping symptoms, diagnosis of the condition is frequently challenging. Exogenous compounds or combinations known as endocrine-disrupting chemicals (EDCs) can imitate the effects of steroid hormones and obstruct their metabolism. EDCs and this condition have recently been the subject of intensive research to better understand the possible contribution of these substances to the pathophysiology of PCOS. It was shown that EDC exposure can be connected to PCOS in either a direct or indirect way since PCOS is linked to higher levels of oxidative stress and inflammation, which lead to obesity, insulin resistance, and infertility. This review's objective is to investigate how exposure to environmental contaminants affects the etiology of polycystic ovarian syndrome.
Purpose:
Methyl triclosan (MTCS) is one of the biomethylated by-products of triclosan (TCS). With the increasing use of TCS, the adverse effects of MTCS have attracted extensive attention in recent years. The purpose of this study was to investigate the cytotoxicity of MTCS and to explore the underlining mechanism using human hepatocyte L02 cells as in vitro model.
Results:
The cytotoxicity results revealed that MTCS could inhibit cell viability, disturb the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG), and reduce the mitochondrial membrane potential (MMP) in a dose-dependent manner. In addition, MTCS exposure significantly promoted the cellular metabolic process, including enhanced conversion of glucose to lactic acid, and elevated content of intracellular triglyceride (TG) and total cholesterol (TC). RNA-sequencing and bioinformatics analysis indicated disorder of glucose and lipid metabolism was significantly induced after MTCS exposure. Protein-protein interaction network analysis and node identification suggested that Serine hydroxy methyltransferase 2 (SHMT2), Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), Asparagine synthetase (ASNS) and Phosphoglycerate dehydrogenase (PHGDH) are potential molecular markers of metabolism imbalance induced by MTCS.
Conclusion:
These results demonstrated that oxidative stress and metabolism dysregulation might be involved in the cytotoxicity of MTCS in L02 cells.
Personal care products (PCPs) are products used in cleaning, beautification, grooming, and personal hygiene. The rise in diversity, usage, and availability of PCPs has resulted in their higher accumulation in the environment. Thus, these constitute an emerging category of environmental contaminants due to the potential of its constituents (chemical and non-chemical) to induce various physiological effects even at lower concentrations (ng/L). For analyzing the impact of the PCPs constituents on the non-target organism about 300 article including research articles, review articles and guidelines were studied from 2000 to 2023. This review aims to firstly discuss the fate and accumulation of PCPs in the aquatic environment and organisms; secondly provides overview of environmental risks that are linked to PCPs; thirdly review the trends, current status of regulations and risks associated with PCPs and finally discuss the knowledge gaps and future perspectives for future research. The article discusses important constituents of PCPs such as antimicrobials, cleansing agents and disinfectants, fragrances, insect repellent, moisturizers, plasticizers, preservatives, surfactants, UV filters, and UV stabilizers. Each of them has been found to display certain toxic impact on the aquatic organisms especially the plasticizers and UV filters. These continuously and persistently release biologically active and inactive components which interferes with the physiological system of the non-target organism such as fish, corals, shrimps, bivalves, algae, etc. With a rise in the number of toxicity reports, concerns are being raised over the potential impacts of these contaminant on aquatic organism and humans. The rate of adoption of nanotechnology in PCPs is greater than the evaluation of the safety risk associated with the nano-additives. Hence, this review article presents the current state of knowledge on PCPs in aquatic ecosystems.
Objective:
To examine the association between urinary levels of triclosan (TCS), a ubiquitous endocrine disrupter, and menopausal status using the National Health and Nutrition Examination Survey.
Methods:
A retrospective cross-sectional study from 2003 to 2016 was conducted among US female participants who completed the reproductive health questionnaire and provided TCS-level measurements. Exposure was assessed by urinary TCS levels adjusted for urinary creatinine; levels were log-transformed to achieve normal distribution for parametric analyses. Menopausal status was based on participants' responses to: "What is the reason that you have not had a period in the past 12 months?" Multivariable linear regression analyses examined the association between creatinine-adjusted urinary TCS levels and menopausal status after adjusting for age at survey completion, body mass index, race, ethnicity, and smoking exposure.
Results:
Of the final sample of female participants (n = 6,958), 40% identified as postmenopausal, of whom 60% had experienced natural menopause, and of these, 11% had become menopausal at under 40 years of age. Triclosan levels correlated positively with advancing age (r = 0.09, P < 0.001) and inversely with body mass index (r = -0.09, P < 0.001). Smoking exposure was associated with significantly lower TCS levels (P < 0.001). Compared with premenopausal women, postmenopausal women had significantly higher log-transformed, creatinine-adjusted TCS levels (mean, -1.22 ± 1.79 vs -1.51 ± 1.79 ng/mg creatinine; P < 0.001). Triclosan levels were unrelated to the duration of menopause and did not differ between women who underwent natural versus surgical menopause, and premature menopause versus menopause at 40 years or older. In unweighted multivariate linear regression analyses, menopausal status was independently associated with higher urinary TCS levels after adjusting for covariates (β coefficient, 0.17; 95% CI, 0.020-0.323; P = 0.026).
Conclusions:
In a nationally representative sample, postmenopausal status was associated with higher urinary TCS levels, observations that merit further investigation into potential exposures and health consequences.
Triclosan, belonging to the bisphenols, is a known antiseptic broad‐spectrum biocide. It has a very wide range of applications, both in health care and in the household. Triclosan enters the environment, both water bodies and soil, because of its high prevalence and the ability to accumulation. Excessive use of antimicrobial formulations may cause the generation of resistance among microorganisms. Reduced susceptibility to triclosan is observed more frequently and in an expanded group of microorganisms and is conditioned by a number of different mechanisms occurring on the molecular level. Conventional wastewater treatment processes are not always able to provide a reliable barrier to triclosan. Therefore, additional advanced treatment technologies are being considered in areas, where a triclosan contamination problem has been identified. Removal of triclosan from wastewater is carried out using different biological and chemical techniques; however, it should be pointed out that physico‐chemical methods often generate toxic by‐products. Toxicity of triclosan and its degradation products, bacterial resistance to this compound, and evident problems with triclosan elimination from wastewater are currently the main problems faced by companies creating products containing triclosan.
Practitioner Points
Triclosan is an emerging pollutant in the environment because of its ability to accumulation and high prevalence.
Reduced susceptibility to triclosan is being observed more frequently.
Conventional wastewater treatment processes are not always able to provide a reliable barrier to triclosan.
Additional advanced treatment technologies should be implemented to remove triclosan from wastewater.
Poly (lactic-co-glycolic acid) (PLGA) Polymer in Development of Delivered Drug Formulations in Current Interest in Pharmaceutical Technology
Triclosan (TCS), an antimicrobial compound, is known to have potential endocrine-disruptive properties, but the underlying toxic mechanisms at the metabolic level are not well understood. Here, we applied metabolomics and lipidomics combined with mass spectrometry imaging (MSI) to unveil the mechanisms of the enhanced growth of MCF-7 breast cancer cell spheroids (CCS) exposed to TCS. To obtain a wide coverage of metabolites and lipids by using MSI, we used techniques of matrix-assisted laser desorption/ionization (MALDI) and MALDI coupled with laser-postionization. The results showed that TCS and TCS sulfate penetrated into the entire area at 0-3 h and both localized in the inner area at 6 h. After 24 h, a portion of two compounds was released from CCS. Omic data indicated that TCS exposure induced alterations via several pathways, including energy metabolism and biosynthesis of glycerophospholipids and glycerolipids. Further MSI data revealed that the enhancement of energy supply in the peripheral area and the increase of energy storage in the inner area might contribute to the enhanced growth of MCF-7 breast CCS exposed to TCS. This study highlights the importance of integrating metabolite distributions and metabolic profiles to reveal the novel mechanisms of TCS-triggered endocrine disrupting effects.
In recent years, triclosan (TCS) has been widely used as an antibacterial agent in personal care products due to the spread of the Coronavirus. TSC is an emerging contaminant, and due to its stability and toxicity, it cannot be completely degraded through traditional wastewater treatment methods. In this study, a novel strain of Enterobacter cloacae was isolated and identified that can grow in high TCS concentrations. Also, we introduced naphthalene dioxygenase as an effective enzyme in TCS biodegradation, and its role during the removal process was investigated along with the laccase enzyme. The change of cell surface hydrophobicity during TCS removal revealed that a glycolipid biosurfactant called rhamnolipid was involved in TCS removal, leading to enhanced biodegradation of TCS. The independent variables, such as initial TCS concentration, pH, removal duration, and temperature, were optimized using the response surface method (RSM). As a result, the maximum TCS removal (97%) was detected at a pH value of 7 and a temperature of 32 °C after 9 days and 12 h of treatment. Gas chromatography-mass spectrometry (GC/MS) analysis showed five intermediate products and a newly proposed pathway for TCS degradation. Finally, the phytotoxicity experiment conducted on Cucumis sativus and Lens culinaris seeds demonstrated an increase in germination power and growth of stems and roots in comparison to untreated water. These results indicate that the final treated water was less toxic.
Objective:
Triclosan (TCS), a novel endocrine disrupter, has induced widespread human exposure due to its widespread use in personal care products. Environmental TCS exposure was suggested to be associated with human semen quality. However, little is known about seminal plasma TCS concentration and the risk of low sperm quality. This case-control study is established to examine the relationship between seminal plasma TCS and the risk of low sperm quality.
Study design:
One hundred men with low sperm quality as cases and one hundred normal men as controls were recruited a fertility clinic in Shijiazhuang, China, during 2018-2019. Seminal plasma TCS concentration was determined using an ultrahigh-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). Sperm concentration, sperm count, sperm motility and sperm progressive motility were evaluated according to World Health Organization (WHO) guidelines to assess the sperm quality. We used the Mann-Whitney rank-sum test and Kruskal-Wallis test to assess the differences of seminal plasma TCS concentration between the cases and the controls. In addition, logistic regression analysis was used to estimate the associations between seminal plasma TCS concentrations and low sperm quality risk adjusting for age, body mass index (BMI), abstinence time, smoking, and drinking RESULTS AND CONCLUSIONS: The level of seminal plasma TCS was observed slightly but not significantly higher in the case group than the control group. We also observed significant association between seminal plasma TCS concentrations and semen parameters in both control and case groups. Moreover, the seminal plasma TCS levels at the fourth quartile were found to be more likely to exhibit low sperm quality risk with increased adjusted odds ratios of 2.36 (95% confidence interval 1.03-5.39) compared to the first quartile. Our results reveal that seminal plasma TCS concentration was positively associated with low sperm quality risk.
Hundreds of xenobiotics, with very diverse origins, have been detected in human milk, including contaminants of emerging concern, personal care products and other current-use substances reflecting lifestyle. The routes of exposure to these chemicals include dermal absorption, ingestion and inhalation. Specific families of chemicals are dominant among human milk monitoring studies (e.g., organochlorine pesticides, bisphenol A, dioxins), even though other understudied families may be equally toxicologically relevant (e.g., food-processing chemicals, current-use plasticizers and flame retardants, mycotoxins). Importantly, the lack of reliable human milk monitoring data for some individual chemicals and, especially, for complex mixtures, is a major factor hindering risk assessment. Non-targeted screening can be used as an effective tool to identify unknown contaminants of concern in human milk. This approach, in combination with novel methods to conduct risk assessments on the chemical mixtures detected in human milk, will assist in elucidating exposures that may have adverse effects on the development of breastfeeding infants.
Triclosan is a chlorinated biphenolic with a broad spectrum of antiseptic activities used in cosmetics and hygiene products. Continuous exposure can lead to the absorption and bioaccumulation of this substance with harmful health effects. In fact, previous studies have shown that Triclosan acts as an endocrine-disrupting chemical on reproductive organs, with consequent negative effects on reproductive physiology. Therefore, to assess potential adverse impacts on fertility, we tested Triclosan on swine granulosa cells, a model of endocrine reproductive cells. We examined its effects on the main features of granulosa cell functions such as cell growth (BrdU incorporation and ATP production) and steroidogenesis (17-β estradiol and progesterone secretion). Moreover, since oxidant–antioxidant balance plays a pivotal role in follicular function, redox status markers (superoxide, hydrogen peroxide and nitric oxide production, enzymatic and non-enzymatic scavenging activity) were studied. Our results show that Triclosan significantly inhibits cell growth (p < 0.001), steroidogenesis (p < 0.001), superoxide and nitric oxide production (p < 0.001), while it increases (p < 0.05) enzymatic defense systems. Collectively, these data suggest a disruption of the main granulosa cell functions, i.e., proliferation and hormone production, as well as and an imbalance in redox status. On these bases, we can speculate that Triclosan would impair granulosa cell functions, thus exerting negative effects on reproductive function. Further studies are needed to explore lower Triclosan concentrations and to unravel its mechanisms of action at gene level.
Several scientific studies have suggested a link between increased exposure to pollutants and a rise in the number of neurodegenerative disorders of unknown origin. Notably, triclosan (an antimicrobial agent) is used in concentrations ranging from 0.3% to 1% in various consumer products. Recent studies have also highlighted triclosan as an emerging toxic pollutant due to its increasing global use. However, a definitive link is missing to associate the rising use of triclosan and the growing number of neurodegenerative disorders or neurotoxicity. In this article, we present systematic scientific evidence which are otherwise scattered to suggest that triclosan can indeed induce neurotoxic effects, especially in vertebrate organisms including humans. Mechanistically, triclosan affected important developmental and differentiation genes, structural genes, genes for signaling receptors and genes for neurotransmitter controlling enzymes. Triclosan‐induced oxidative stress impacting cellular proteins and homeostasis which triggers apoptosis. Though the scientific evidence collated in this article unequivocally indicates that triclosan can cause neurotoxicity, further epidemiological studies may be needed to confirm the effects on humans. Molecular targets of triclosan‐induced neurotoxicity.
Antimicrobial triclosan (TCS), one of the popular ingredients added to sanitizing products, has widespread use in personal care. However, it poses potential risks to reproduction and development. Unfortunately, the underlying mechanisms remain largely unclear. This study aimed to investigate effects of TCS on the development of preimplantation mouse embryo and explore related mechanisms Mouse zygotes were collected and cultured to blastocysts in KSOM medium supplemented with four different concentrations of TCS. The development rates, pluripotency or stem cells markers, and microRNA (miR)-134 were compared between control and experimental groups across each specific developmental stage. Prolonged exposure to TCS remarkably impaired early embryo development in vitro by hampering morula and blastocyst formations (P < 0.05, P < 0.001). The arrest of embryo development was linked with decreased expressions of pluripotency or stem cells markers, especially Nanog and Notch1. Moreover, based on miRWalk database and in vitro luciferase assays, we confirmed that miR-134 induced by TCS was a negative regulator of Nanog. Crucially, impaired TCS-treated embryos could be rescued by inhibiting miR-134 or forced overexpressing Nanog mRNA. Altogether, our results highlight that pathologically relevant level of TCS compromises preimplantation mouse embryo development by inducing miR-134 and triggering miR-134/Nanog axis. Considering high conservative of miR-134 between human and mouse, it should be the most promising potential target to regulate development of preimplantation embryo.
Prenatal triclosan (TCS) exposure has been reported to be associated with various birth outcomes and thyroid function, while the study of TCS exposure for congenital heart disease (CHD) patients is limited. In the present study, paired mother-fetus blood samples from CHD and healthy participants were collected to measure TCS exposure levels, and then check their relationship. Coupled with the concentrations of thyroid function biomarkers [free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid antibodies (TgAb)] in maternal blood, we aimed to investigate whether the hormone-disrupting properties of TCS will affect its association with CHD. Our results indicated that the maternal TCS concentrations in the CHD group (median 0.31 ng/mL) were significantly lower than those in the control group (0.48 ng/mL, Mann Whitney U test, p = 0.01). Higher interquartile of TCS levels in maternal blood was associated with decrease odds of CHD (adjusted OR = 0.61, 95%CI: 0.41–0.91, p = 0.02). Maternal blood TCS higher than the cut-off value (25th quantile, 0.17 ng/mL) was significantly negatively associated with CHD risk (adjusted OR = 0.24, 95%CI: 0.09–0.62, p < 0.01). Besides, none of the thyroid biomarkers were significantly associated with maternal TCS exposure. However, maternal FT4 concentrations were positively correlated with TCS transplacental transfer rate and cord blood TCS levels (general linear regression, both p < 0.01). The results of molecular docking and dynamics simulation suggested that these correlations might be related to the transthyretin, a thyroid hormone-binding protein involved in the placental thyroid hormone transport system. Overall, our findings indicated that at normal exposure levels, the increase of maternal blood TCS concentration may have an inverse association with CHD, which merits further investigation.
Little is known about effects of public use of antimicrobial handwashing soap. A double-blinded, randomized clinical trial of hands of primary caretakers in 238 inner city households was conducted in which effects of plain or antimicrobial (containing 0.2% triclosan) handwashing soap on bacterial counts of the hands were compared before and after a single wash and before and after handwashing following a year of product use. The randomly assigned product was provided without cost to each household during monthly home visits, and compliance with product use was monitored. Households were contacted by telephone weekly and with a home visit monthly for 11 months. Hand cultures were obtained before and after handwashing at baseline and after 11 months, using a modified glove juice technique.
Overall, there were no significant differences in pre-to-post handwashing counts at baseline (p = 0.41), but by the end of one year, post-wash counts were significantly lower than pre-wash (p = 0.000) for those using either antimicrobial or plain soap. There were no significant differences in mean log counts either before or after handwashing between those using the antimicrobial or plain soap at baseline or after a year of use (all p values >0.28). For the group using antimicrobial soap, higher counts were observed post-handwashing in 31.3% of paired samples at baseline and 26.7% after one year (p = 0.03). A single handwash had minimal effect on quantity of hand flora, but there were significant effects over time, regardless of whether antimicrobial or plain soap was used. In the absence of more definitive evidence, the risk-benefit ratio argues in favor of targeted rather than ubiquitous, general household use of antimicrobial soap.
The aim of this study was to determine human prenatal and postnatal exposures to polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), hydroxylated metabolites of PCBs (polychlorobiphenylols; OH-PCBs), and pentachlorophenol (PCP). The median PBDE fresh-weight concentrations in maternal and cord blood plasma and in breast milk were 24, 4.3, and 75 pg/g, respectively. The PCB concentrations were approximately 60 times higher in each compartment (1,560, 277, and 4,310 pg/g, respectively). Calculated on a lipid weight basis, the levels were comparable in maternal blood plasma and breast milk. In contrast to PCBs, differences were found between PBDE congener distribution in maternal and cord blood plasma. The OH-PCBs constituted up to 26% of the PCB levels in maternal blood plasma and 53% in cord blood plasma, with levels of 120 and 88 pg/g fresh weight, respectively, and in breast milk 3 pg/g. The corresponding concentrations for PCP were 2,830, 1,960, and 20 pg/g. The ratios of PCB to OH-PCB were 13, 3, and 1,400 in maternal, cord plasma, and breast milk, respectively. It is evident that prenatal exposures occur for all the analytes. Moreover, the exposure continues after birth via breast milk. However, levels of OH-PCBs and PCP in breast milk are low compared with levels in blood plasma. Exposures to both PCBs and PBDEs, and in particular to the endocrine-active halogenated phenolic compounds, are of concern and implicate a potential risk for developmental disturbances.
The number of personal hygiene products containing triclosan has increased rapidly during the last decade, and triclosan is one of the most common antibacterial compounds used in dentifrices today. However, the extent of triclosan exposure has not yet been well described. The potential risks of generating triclosan-resistant pathogenic microorganisms or of the selection of resistant strains are some areas of concern. The aim of the present study was to (1) obtain information on baseline levels of triclosan in plasma and urine, and (2) study the pharmacokinetic pattern of triclosan after a single-dose intake. Ten healthy volunteers were exposed to a single oral dose of 4 mg triclosan by swallowing an oral mouthwash solution. Triclosan in plasma and urine was followed before and up to 8 d after exposure. Triclosan levels in plasma increased rapidly, with a maximum concentration within 1 to 3 h, and the terminal plasma half-life was 21 h. The major fraction was excreted within the first 24 h. The accumulated urinary excretion varied between the subjects, with 24 to 83% of the oral dose being excreted during the first 4 d after exposure. In conclusion, triclosan appears to be readily absorbed from the gastrointestinal tract and has a rapid turnover in humans. The high lipid solubility of the substance gives rise to questions regarding distribution properties and accumulation. The findings of the present study form a basis for greater understanding of the toxicokinetic properties of triclosan in humans.
We studied the effects of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) on the kinetics of the cytochrome P450 (P450)-dependent monooxygenases in rat liver microsomes. The activities of 7-ethoxyresorufin O-deethylase (EROD) and 7-pentoxyresorufin O-depentylase (PROD) in rat liver microsomes exposed to 3-methylcholanthrene (MC) and phenobarbital (PB) respectively, were substantially inhibited by Irgasan DP300. The inhibition profile of EROD was competitive, whereas that of PROD was noncompetitive; the Ki values from Hanes plots were 0.24 and 1.48 microM for EROD and PROD, respectively. Phenacetin O-deethylase (PCOD) and 4-nitrophenol hydroxylase (4NPH) activities in rats exposed to PB were also inhibited by Irgasan DP300, at Ki values lower than those for other microsomes. Irgasan DP300 slightly inhibited testosterone 6 beta-hydroxylase (TS6BH) activities in some microsomes. No effect of Irgasan DP300 on lauric acid omega-hydroxylase (LAOH) activity was evident in any microsomal preparations. These results indicated that Irgasan DP300 inhibits MC- and PB-inducible P450-dependent monoxygenase in vitro competitively or noncompetitively, and that the P450 enzymes of the CYP1A or CYP2B subfamily may contribute to Irgasan DP300 toxicity.
Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a nonionic, broad spectrum, antimicrobial agent that, because of its favorable safety profile, has been incorporated into a variety of many personal care products, including deodorant soaps, underarm deodorants, shower gels, and health care personnel handwashes. Triclosan exhibits a moderate degree of substantivity to the skin, and, in many products, it imparts a remnant antimicrobial effect. Although direct contact with the material under exaggerated exposure conditions causes dermal irritation in laboratory animals, it has only rarely been associated with skin irritation or sensitization in human being in formulated products. Acute, subacute/subchronic, and chronic toxicity profiles have been established to determine that triclosan is neither an acute oral toxicant nor that it acts as a carcinogen, mutagen, or teratogen. A new application for triclosan is in oral dentifrices for plaque control. Currently under investigation in the United States, it is approved for oral care application in Canada and many European countries.
Earlier studies in our laboratory showed that hydroxylated metabolites of polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) competitively inhibit thyroxine (T4) binding to transthyretin (TTR) and type I deiodinase (D1) activity. In this study, we investigated the possible inhibitory effects of hydroxylated metabolites of polyhalogenated aromatic hydrocarbons (PHAHs) on iodothyronine sulfotransferase activity. Rat liver cytosol was used as a source of sulfotransferase enzyme in an in vitro assay with 125I-labeled 3,3'-diiodothyronine (T2) as a model substrate. Increasing amounts of hydroxylated PCBs, PCDDs, or PCDFs or extracts from incubation mixtures of PHAHs and induced liver microsomes were added as potential inhibitors of T2 sulfotransferase activity. Hydroxylated metabolites of PCBs, PCDDs, and PCDFs were found to be potent inhibitors of T2 sulfotransferase activity in vitro with IC50 values in the low micromolar range (0.2-3.8 microM). The most potent inhibitor of T2 sulfotransferase activity in our experiments was the PCB metabolite 3-hydroxy-2,3',4, 4',5-pentachlorobiphenyl with an IC50 value of 0.2 microM. A hydroxyl group in the para or meta position appeared to be an important structural requirement for T2 sulfotransferase inhibition by PCB metabolites. Ortho hydroxy PCBs were much less potent, and none of the parent PHAHs was capable of inhibiting T2 sulfotransferase activity. In addition, the formation of T2 sulfotransferase-inhibiting metabolites of individual brominated diphenyl ethers and nitrofen as well as from some commercial PHAH mixtures (e.g., Bromkal, Clophen A50, and Aroclor 1254) was also demonstrated. These results indicate that hydroxylated PHAHs are potent inhibitors of thyroid hormone sulfation. Since thyroid hormone sulfation may play an important role in regulating free hormone levels in the fetus, and PCB metabolites are known to accumulate in fetal tissues after maternal exposure to PCBs, these observations may have implications for fetal thyroid hormone homeostasis and development.
triclosan is widely used in many products that contact the skin of consumers. This study compares in vivo and in vitro skin absorption of triclosan and determines the potential of skin to metobolize it prior to entering the blood stream. After in vivo topical application of a 64.5mM alcoholic solution of [(3)H]triclosan to rat skin, 12% radioactivity was recovered in the faeces, 8% in the carcass 1% in the urine, 30% in the stratum corneum and 26% was rinsed from the skin surface at 24 hours after application. Free triclosan and the glucuronide and sulfate conjugates of triclosan were found in urine and faeces. triclosan penetrated rat skin more rapidly and extensively than human skin in vitro. 23% of the dose had penetrated completely through rat skin into the receptor fluid by 24 hours, whereas penetration through human skin was only 6.3% of the dose. Chromatographic analysis of the receptor solutions showed that triclosan was metabolized to the glucuronide, and to a lesser extent to the sulfate, during passage through the skin. triclosan glucuronide appeared rapidly in the receptor fluid whereas triclosan sulfate remained in the skin. Although the major site of metabolism was the liver, conjugation of triclosan in skin was also demonstrated in vitro and in vivo, particularly to the glucuronide conjugate which was more readily removed from the skin. The in vitro system provides a reasonable estimate of dermal absorption in vivo for the rat. Therefore by extrapolation of the comparative in vitro data for human and rat skin it is reasonable to deduce that dermal absorption in human of triclosan applied at the same dose is about one-third of that in the rat in vivo.
Consumer antibacterial soaps contain triclosan or triclocarban. No scientific data have been published to suggest that the use of antibacterial agents in household products prevents infection, and triclosan resistance mechanisms have recently been identified. Little data are available regarding the prevalence of antibacterial agents contained in consumer soaps.
In a physician-performed survey of 23 stores in 10 states from December 1999 to April 2000, investigators determined the number of national brand liquid and bar soaps and percent of each containing antibacterial agents sold at national chain, regional grocery, and Internet stores.
Antibacterial agents were present in 76% of liquid soaps and 29% of bar soaps available nationally. There were no differences found between national, regional, and Internet stores.
Overall, 45% of surveyed soaps contain antibacterial agents. With limited documented benefits and experimental laboratory evidence suggesting possible adverse effects on the emergence of antimicrobial resistance, consumer antibacterial use of this magnitude should be questioned.
A growing number of studies have reported phenolic halogenated compounds (PHCs) that are retained in the blood of humans and wildlife. These PHCs may be industrial chemicals; metabolites thereof, as in the case with polychlorobiphenylols (OH-PCBs); or of natural origin. The present study was aimed to identify hitherto unknown PHCs in human plasma with chemical structures that are consistent to PHCs known to possess endocrine-disrupting activity. For this purpose, samples of blood plasma from 10 randomly selected male blood donors from Sweden were pooled and analyzed by GC/ECD and GC/MS. Brominated, bromochlorinated, and chlorinated methyl derivatives of phenols and OH-PCBs were synthesized to be used as authentic reference standards. More than 100 PHCs were indicated in the plasma, and among those a total of 9 monocyclic brominated or chlorinated phenol-, guaiacol-, and/or catechol-type compounds were identified as their methylated derivatives. The two major compounds were 2,4,6-tribromophenol and pentachlorophenol. Thirty-eight OH-PCB congeners were structurally identified on two GC columns of different polarity. The origin of the OH-PCB metabolites in the context of their parent PCB congeners are suggested. Other PHCs identified in the male plasma were Triclosan (5-chloro-2-[2,4-dichlorophenoxy] phenol), a common bactericide; 4-hydroxy-heptachlorostyrene, a metabolite of octachlorostyrene; and 3,5-dibromo-2-(2,4-dibromophenoxy)phenol, a natural compound and a potential metabolite of polybrominated diphenyl ethers.
To demonstrate through clinical pharmacokinetic studies that triclosan does not accumulate in blood or plasma in human subjects who regularly use triclosan-containing dentifrice.
Three clinical pharmacokinetic studies were conducted to assess the blood or plasma levels of triclosan following toothbrushing with dentifrice formulations containing triclosan. In Study 1, both a single-dose and a multiple-dose phase were conducted. In the single-dose phase, subjects brushed one time with 1.25 g dentifrice containing 0.3% triclosan (3.75 mg triclosan dose) and ingested all of the dentifrice. Blood samples were collected at multiple time points from pre-dose to 72 hrs post-dose and analyzed for total triclosan levels. In the multiple-dose phase, these same subjects brushed three times daily as in the single-dose phase. This pattern was followed for 12 consecutive days. Blood samples were taken for triclosan analysis at multiple time points up to 48 hrs after the first dose of day 12. Study 2 was a parallel, open-labeled clinical study to compare triclosan blood levels from twice daily brushing with 1 gm of dentifrice containing 0.2% triclosan to twice daily ingestion of 20 ml of a 0.01% triclosan aqueous solution over a period of 21 days. Blood samples were taken for triclosan analysis at baseline and at 4 hrs after the morning dose on days 7, 14, and 21. Study 3 was a parallel, double-blind, 12-wk brushing study with dentifrice containing 0.2% triclosan or a matching placebo. Blood samples were taken for triclosan analysis at baseline and at 3 and 12 wks at 4 hrs after the morning dose.
In the single-dose study, Triclosan was absorbed into the systemic circulation with a T(1/2) of the terminal plasma concentration ranging between 6-63 hrs. The mean AUC(0-inf) after a single dose was found to be 2,809 ng x hr/ml. After 12 days of three times daily toothbrushing and ingestion of the dental slurry, the mean triclosan plasma concentration was 352 ng/ml in the steady state period, and the mean AUC in a 24-hr period (AUC24) was found to be 8,460 ng x hr/ml. This AUC24 was normalized for the number of brushings for comparison to the AUC(0-inf) after a single brushing. There was no significant (P = 0.93) difference between these AUC values suggesting a complete elimination of daily triclosan dose and no increase in the triclosan level during repeated brushing/ingestion. In the two other dentifrice studies, the triclosan blood concentration appeared to reach a steady state level by day 7 and was maintained at the steady state level (14 to 21 ng/ml) for up to 12 wks. These results support the conclusion that the elimination of a daily triclosan dose is complete and no accumulation of triclosan was observed even after three times daily toothbrushing with 1.25 g dentifrice containing 0.3% triclosan and full ingestion of the dentifrice.
To determine clinically the buccal absorption and plaque retention of triclosan from a mouthrinse containing 0.03% triclosan.
15 ml of the triclosan oral rinse (N=9) or placebo mouthrinse (N=12) was used twice daily for 21 days in humans. Blood, dental plaque and the expectorated oral rinse were collected prior to, during the treatment period at given intervals, and 8 days after the treatment. Dental plaque and blood samples were collected 1 hr and 4 hr after the morning rinse, respectively. The oral retention of triclosan was calculated by subtracting the amount of triclosan recovered in the expectorate from the triclosan dose applied (4.50 mg) in the mouthrinse. Plasma samples were analyzed for free triclosan (the parent molecule) and its glucuronide and sulfate conjugates, whereas dental plaque was analyzed only for total triclosan.
No significant treatment-related adverse effects were observed during the clinical phase of the study. The average daily oral retention of triclosan was calculated to be 0.660 mg, which is 7.33% of the triclosan dose applied (2 x 4.50 mg). Plaque contained an average 20.5-46.4 microg of triclosan per g of plaque collected. At various sampling times, mean plasma concentrations were: no detectable triclosan, 63.8-86.3 microg/ml of triclosan glucuronide and 8.23-18.0 ng/ml of triclosan sulfate. The mean total triclosan plasma concentration ranged from 74.5 to 94.2 microg/ml with plateau concentrations reached after 2 days of dosing. Eight days after the last treatment the triclosan plasma concentration returned to baseline levels (< 2 ng/ml).
High levels of the commonly used, effective bactericide Triclosan was found in three out of five randomly selected human milk samples. It was also found in the bile of fish exposed to municipal wastewater and in wild living fish from the receiving waters of the three wastewater treatment plants.
Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is an antibacterial agent included in dentifrices and mouth rinses. Previously, we reported that triclosan reduces the production of the inflammatory mediators in gingival fibroblasts. The aim of this study was to investigate the uptake, distribution, and release of (14)C-triclosan in gingival fibroblasts. Time-course studies showed that the uptake of (14)C-triclosan in cytoplasmic and nuclear fraction started within the first minute of incubation, increased gradually, and reached constant levels after 1 h in the nuclear fraction and slightly increased in the cytoplasmic fraction between 3 and 24 h. The distribution of (14)C-triclosan in the cytoplasmic and the nuclear fractions was, on an average, 84 and 16%, respectively. Autoradiographic results based on transmission electron microscopy confirmed the distribution of (14)C-triclosan in the cytoplasm and nucleus of the cell. The release of (14)C-triclosan showed that the radioactivity of the agent in the medium gradually increased during the first hour of incubation and then reached steady-state levels. After repeated washing of preloaded fibroblasts, the level of (14)C-triclosan in the cytoplasmic fraction decreased by 77% whereas the level in the nuclear fraction remained unchanged. Our results demonstrate that triclosan is distributed in the cytoplasm and remains associated with the nucleus of gingival fibroblasts, suggesting that the agent may affect the intracellular signal pathways involved in the production of inflammatory mediators.
Triclosan is a broad spectrum antibacterial agent used in many household products. Due to its structural similarity to polychlorobiphenylols, which are potent inhibitors of the sulfonation and glucuronidation of 3-hydroxy-benzo[a]pyrene, it was hypothesized that triclosan would inhibit these phase II enzymes. This study was designed to assess the interactions of triclosan as a substrate and inhibitor of 3'-phosphoadenosine 5'-phosphosulfate-sulfotransferases and UDP-glucuronosyltransferases in human liver cytosol and microsomes. Triclosan was sulfonated and glucuronidated in human liver. The apparent Km and Vmax values for triclosan sulfonation were 8.5 microM and 0.096 nmol/min/mg protein, whereas Km and Vmax values for glucuronidation were 107 microM and 0.739 nmol/min/mg protein. Triclosan inhibited the hepatic cytosolic sulfonation of 3-hydroxybenzo(a)pyrene (3-OH-BaP), bisphenol A, p-nitrophenol, and acetaminophen with IC50 concentrations of 2.87, 2.96, 6.45, and 17.8 microM, respectively. Studies of 3-OH-BaP sulfonation by expressed human SULT1A1*1, SULT1A1*2, SULT1B1, and SULT1E1 showed that triclosan inhibited the activities of each of these purified enzymes with IC50 concentrations between 2.09 and 7.5 microM. Triclosan was generally a less potent inhibitor of microsomal glucuronidation. IC50 concentrations for triclosan with 3-OH-BaP, acetaminophen, and bisphenol A as substrates were 4.55, 297, and >200 microM, respectively. Morphine glucuronidation was not inhibited by 50 microM triclosan. The kinetics of 3-OH-BaP sulfonation and glucuronidation were examined in the presence of varying concentrations of triclosan: the inhibition of sulfonation was noncompetitive, whereas that of glucuronidation was competitive. These findings reveal that the commonly used bactericide triclosan is a selective inhibitor of the glucuronidation and sulfonation of phenolic xenobiotics.
The pregnane X receptor (PXR) mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification. The receptor is expressed in liver and intestinal tissues and is activated by a wide range of compounds. The ability of a diverse range of dietary compounds to activate PXR-mediated transcription was assayed in HuH7 cells following transient transfection with human PXR (hPXR). The compounds investigated included phytochemicals such as lignans and phytoestrogens, organochlorine dietary contaminants such as polychlorinated biphenyls (PCBs) and triclosan and selected steroid, drug and herbal compounds. The hPXR activation at the top concentrations tested (10 microM) relative to the positive control 10 microM rifampicin ranged from 1.3% (trans-resveratrol) to 152% (ICI 182780). Hydroxylated compounds were marginally more potent than the parent compounds (tamoxifen activation was 74.6% whereas 4 hydroxytamoxifen activation was 84.2%) or significantly greater (vitamin D3 activation was 1.6%, while hydroxylated vitamin D3 activation was 55.6%). Enterolactone, the metabolite of common dietary lignans, was a medium activator of PXR (35.6%), compared to the lower activation of a parent lignan, secoisolariciresinol (20%). Two non-hydroxylated PCB congeners (PCB 118 and 153), which present a larger fraction of the PCB contamination of fatty foods, activated hPXR by 26.6% and 17%, respectively. The pesticide trans-nonachlor activation was 53.8%, while the widely used bacteriocide triclosan was a medium activator of hPXR at 46.2%. The responsiveness of PXR to activation by lignan metabolites suggests that dietary intake of these compounds may affect the metabolism of drugs that are CYP3A substrates. Additionally, the evidence that organochlorine chemicals, particularly the ubiquitous triclosan, activate hPXR suggests that these environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid hormone metabolism with potential adverse health effects in exposed individuals.
Adverse effects in infants due to the ingestion of drugs and other xenobiotics remain an area of concern. A key parameter in assessing infant exposure via breast milk, the milk to plasma concentration ratio (M/P), has not been determined in vivo in humans for most drugs. There are various methods for predicting M/P, which involve in vitro experiments in mammary cell monolayers, assessment of drug binding to plasma and milk protein and lipid, in vivo experiments in animals, and regression models based on a compound's physicochemical characteristics. This article reviews these approaches in terms of their utility, advantages and disadvantages. Some combination of these methods is necessary for reasonably accurate prediction of M/P in humans.
A sensitive method for the determination of triclosan in plasma and milk is presented. Following hydrolysis of possible conjugates, triclosan is extracted with n-hexane/acetone, partitioned into alcoholic potassium hydroxide, and converted into its pentafluorobenzoyl ester. After sulfuric acid cleanup, sample extracts are analyzed by gas chromatography/electron capture negative ionization mass spectrometry. The limit of quantification was 0.009 ng/g for a 5-g plasma sample and 0.018 ng/g for a 3-g milk sample. The coefficient of variation for the method was 6%. The method was tested on more than 70 human plasma and milk samples, of which all plasma samples and more than half of the milk samples were above the limit of quantification. The presented method has lowered the limit of quantification for triclosan in human matrixes significantly as compared to previous methods and makes possible the analysis of triclosan in humans under normal exposure conditions.
Risker och nytta med triklosan i tandkräm [Risks and benefits with triclosan containing toothpastes]
- S Edwardsson
- L M Burman
- Backman
Edwardsson S, Burman L, Adolfsson-Erici M, Backman N. Risker och nytta med triklosan i tandkräm [Risks and benefits with triclosan containing toothpastes]. Tandlakartidningen 2005;97:58–64.
Determination of triclosan as its pentafluorobenzoyl ester in human plasma and milk using electron capture negative ionization mass spectrometry Clinical evidence for the lack of triclosan accumulation from daily use in dentifrices
- M Allmyr
- Mclachlan Ms
- G Sandborgh-Englund
- Dm Bagley
- Lin
- Yj
Allmyr M, McLachlan MS, Sandborgh-Englund G, Adolfsson-Erici M. Determination of triclosan as its pentafluorobenzoyl ester in human plasma and milk using electron capture negative ionization mass spectrometry. Anal Chem 2006, ___________________ doi:10.1021/ac060666x. Bagley DM, Lin YJ. Clinical evidence for the lack of triclosan accumulation from daily use in dentifrices. Am J Dent 2000;13: 148–52.
Screening av triclosan och vissa bromerade fenoliska ämnen i Sverige. [Screening of triclosan and some brominated, phenolic compounds in Sweden
- Remberger M J Sternbeck
- Strömberg
Remberger M, Sternbeck J, Strömberg K. Screening av triclosan och vissa bromerade fenoliska ämnen i Sverige. [Screening of triclosan and some brominated, phenolic compounds in Sweden]. IVL Rapp 2002:B1477-2.
Risker och nytta med triklosan i tandkräm [Risks and benefits with triclosan containing toothpastes]
- Edwardsson
Screening av triclosan och vissa bromerade fenoliska ämnen i Sverige. [Screening of triclosan and some brominated, phenolic compounds in Sweden]
- Remberger