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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). ...
... • damage or inhibition of cell wall synthesis, which is crucial for the life and survival of the bacterial species; • inhibition of cell membrane function, which can disregulate intra-and extracellular material flow and leak solutes important for cell survival; • inhibition of protein synthesis, which is the basis of enzymes and cell structures, leading to the death of the organism or inhibition of its growth and multiplication; • inhibition of the synthesis of nucleic acids (DNA and RNA) due to the binding of certain antimicrobial agents and inhibition of other metabolic processes, e.g., disruption of the folic acid pathway, which is necessary for bacteria to produce precursors important for DNA synthesis [63,64]. Active substances usually applied to the surface of textiles can be used, e.g., quaternary ammonium compounds, triclosan, and metal salts (such as copper, zinc, and silver) as such and in the form of natural polymers [65,66]. Quaternary ammonium compounds which have a positive charge on the N atom in solution are usually attached to the anionic surface of the fiber by ionic interaction. ...
... Due to the antibiotic resistance of pathogenic bacteria, antimicrobial compounds Active substances usually applied to the surface of textiles can be used, e.g., quaternary ammonium compounds, triclosan, and metal salts (such as copper, zinc, and silver) as such and in the form of natural polymers [65,66]. Quaternary ammonium compounds which have a positive charge on the N atom in solution are usually attached to the anionic surface of the fiber by ionic interaction. ...
Biopolymer composites have received increasing attention for their beneficial properties such as being biodegradable and having less influence to the environment. Biodegradability of materials has become a desired feature due to the growing problems connected with waste management. The aim of the paper is to emphasize the importance of biodegradable textile materials, especially nonwoven materials with an anti-pathogenic layer. The article refers to the definitions of biodegradation, degradation and composting processes, as well as presenting methods of testing biodegradability depending on the type of material. The study gives examples of biodegradation of textiles and presents examples of qualitative and quantitative methods used for testing antimicrobial activity of biodegradable nonwovens with an anti-pathogenic layer.
... Triclosan (TCS), a chlorophenol, is a broad-spectrum antibacterial agent which is widely used in personal care products such as antibacterial soaps and toothpaste (Fang et al. 2010;Witorsch and Thomas 2010). In many studies, TCS has been found in human breast milk (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Toms et al. 2011), blood (Allmyr et al. 2006(Allmyr et al. , 2008, urine (Heffernan et al. 2015;Philippat et al. 2013;Provencher et al. 2014;Yin et al. 2016), and amniotic fluid (Philippat et al. 2013). In 2016, the U.S. Food and Drug Administration (FDA) banned the antimicrobial TCS for use in soaps (Weatherly and Gosse 2017), although it is still widely used in toothpaste and mouthwash. ...
... Triclosan (TCS), a chlorophenol, is a broad-spectrum antibacterial agent which is widely used in personal care products such as antibacterial soaps and toothpaste (Fang et al. 2010;Witorsch and Thomas 2010). In many studies, TCS has been found in human breast milk (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Toms et al. 2011), blood (Allmyr et al. 2006(Allmyr et al. , 2008, urine (Heffernan et al. 2015;Philippat et al. 2013;Provencher et al. 2014;Yin et al. 2016), and amniotic fluid (Philippat et al. 2013). In 2016, the U.S. Food and Drug Administration (FDA) banned the antimicrobial TCS for use in soaps (Weatherly and Gosse 2017), although it is still widely used in toothpaste and mouthwash. ...
Ambient airborne particular matter (PM) is a major environmental risk to human health in the world. Numerous epidemiological, clinical and experimental studies have demonstrated the association between high exposure levels of PM and an increase in various diseases, including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer, neurodegenerative diseases, heart diseases, and diabetes. The proposed underlying biological and molecular mechanisms whereby PM causes adverse health effects include oxidative stress, inflammation and genotoxicity. This chapter provides an overview of the recent literature reporting new insights about the molecular mechanisms linking ambient PM exposure and health effects.
... Triclosan (TCS), a chlorophenol, is a broad-spectrum antibacterial agent which is widely used in personal care products such as antibacterial soaps and toothpaste (Fang et al. 2010;Witorsch and Thomas 2010). In many studies, TCS has been found in human breast milk (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Toms et al. 2011), blood (Allmyr et al. 2006(Allmyr et al. , 2008, urine (Heffernan et al. 2015;Philippat et al. 2013;Provencher et al. 2014;Yin et al. 2016), and amniotic fluid (Philippat et al. 2013). In 2016, the U.S. Food and Drug Administration (FDA) banned the antimicrobial TCS for use in soaps (Weatherly and Gosse 2017), although it is still widely used in toothpaste and mouthwash. ...
... Triclosan (TCS), a chlorophenol, is a broad-spectrum antibacterial agent which is widely used in personal care products such as antibacterial soaps and toothpaste (Fang et al. 2010;Witorsch and Thomas 2010). In many studies, TCS has been found in human breast milk (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Toms et al. 2011), blood (Allmyr et al. 2006(Allmyr et al. , 2008, urine (Heffernan et al. 2015;Philippat et al. 2013;Provencher et al. 2014;Yin et al. 2016), and amniotic fluid (Philippat et al. 2013). In 2016, the U.S. Food and Drug Administration (FDA) banned the antimicrobial TCS for use in soaps (Weatherly and Gosse 2017), although it is still widely used in toothpaste and mouthwash. ...
Pharmaceuticals and personal care products (PPCPs) are emerging contaminants present in the environment. The general population is inevitably exposed to PPCPs in daily life. The PPCP family contains two types of chemicals: pharmaceuticals and personal care products. Pharmaceuticals are used primarily to prevent or treat human and animal diseases, whereas personal care products are used to improve the quality of daily life and include products such as toothpaste, shampoo, lotions, cosmetics, and hair colors. Due to the structural similarity to biologically active compounds, PPCPs have raised public concerns regarding their possible effects on human health and the environment. Over the past two decades, many studies have found that PPCPs are endocrine-disrupting chemicals (EDCs) with profound adverse effects on the endocrine system. Therefore, in this chapter, we discuss several typical PPCPs, such as bisphenol A and its analogues, triclosan, triclocarban, and phthalates, their adverse endocrine-disrupting activities and three typical endocrine system-related modes of action (MOAs) through interaction with estrogen, androgen, and thyroid receptors.
... 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.
... TCS can be absorbed through several routes, including the mucous membrane of the oral cavity, dermal exposure, or the gastrointestinal tract. Considering that most products containing TCS are used for dermal application, its main route of absorption is the skin, through which it is rapidly absorbed due to its lipophilic properties [35] (Table 3). Additionally, Wu et al. noted that TCS can also be absorbed orally which leads to the detection of metabolites in plasma, and also through the gastrointestinal tract [32]. ...
Hygiene is essential to avoid diseases, and this is thanks to daily cleaning and disinfection habits. Currently, there are numerous commercial products containing antimicrobial agents, and although they are efficient in disinfecting, it is still not known the effect of the constant use of these products on human health. In fact, a massive use of disinfectants has been observed due to COVID-19, but the possible adverse effects are not yet known. Triclosan is one of the antimicrobial agents used in cosmetic products, toothpaste, and disinfectants. This compound is an endocrine disruptor, which means it can interfere with hormonal function, with its estrogenic and androgenic activity having already been stated. Even if the use of triclosan is well-regulated, with the maximum allowed concentration in the European Union of 0.3% (m/m), its effects on human health are still uncertain. Studies in animals and humans suggest the possibility of harmful health outcomes, particularly for the reproductive system, and in a less extent for the cardiovascular and thyroid functions. Thus, the purpose of this review was to analyse the possible implications of the massive use of triclosan, mainly on the reproductive and cardiovascular systems and on the thyroid function, both in animals and humans.
... Maternal exposures to air, soil, water, food, clothes, personal care products (e.g., triclosan in toothpaste), dental amalgam (mercury), electronics, and furniture are part of the maternal environment and potential exposure sources. Geographical location (e.g., living near a point source of environmental chemicals) can lead to differential exposure (47,129,130). A recent systematic review based on 20 studies concluded that smoking was inversely associated with HM lipids, energy, and proteins (131). ...
National health and nutrition monitoring is an important federal effort in the U.S. and Canada, and the basis for many of their nutrition and health policies. Understanding of child exposures through human milk (HM) remains out of reach due to lack of current and representative data on its composition and intake volume. This paper provides an overview of the current national health and nutrition monitoring activities for HM-fed children, HM composition (HMC) and volume data used for exposure assessment, categories of potential measures in HM and associated variability factors. In this perspective, we advocate for a framework for collection and reporting of HMC data for national health and nutrition monitoring and programmatic needs, including a shared vision for a publicly available Human Milk Composition Data Repository (HMCD-R) to include essential meta-data associated with HMC. HMCD-R can provide a central, integrated platform for researchers and public health officials for compiling, evaluating, and sharing HMC data. The compiled compositional and metadata in HMCD-R would provide pertinent measures of central tendency and variability and allow use of modeling techniques to approximate compositional profiles for sub-groups, providing more accurate exposure assessments for purposes of monitoring and surveillance. HMC and related metadata could facilitate understanding the complexity and variability of HM composition, provide crucial data for assessment of infant and maternal nutritional needs, and inform public health policies, food and nutrition programs, and clinical practice guidelines.
... TCS is used as an antimicrobial agent in some soaps, personal care products, and toothpastes (Rodricks et al., 2010). Dermal contact from soaps and other personal care products and ingestion (via toothpaste) are the primary routes of exposure to triclosan (Allmyr et al., 2006;Dann and Hontela, 2011). In 2016, triclosan was banned in over-the-counter handwashing soaps (FDA, 2016) and in 2017 it was further banned from any over-the-counter antiseptic products (FDA, 2017). ...
Silicone wristbands act as passive environmental samplers capable of detecting and measuring concentrations of a variety of chemicals. They offer a noninvasive method to collect complex exposure data in large-scale epidemiological studies. We evaluated the inter-method reliability of silicone wristbands and urinary biomarkers in the New Hampshire Birth Cohort Study. A subset of study participants (n = 96) provided a urine sample and wore a silicone wristband for 7 days at approximately 12 gestational weeks. Women were instructed to wear the wristbands during all their normal activities. Concentrations of urinary compounds and metabolites in the urine and parent compounds in wristbands were compared. High detection rates were observed for triphenyl phosphate (76.0%) and benzophenone (78.1%) in wristbands, although the distribution of corresponding urinary concentrations of chemicals did not differ according to whether chemicals were detected or not detected wristbands. While detected among only 8.3% of wristbands, median urinary triclosan concentrations were higher among those with detected wristbands (9.04 ng/mL) than without (0.16 ng/mL). For most chemicals slight to fair agreement was observed across exposure assessment methods, potentially due to low rates of detection in the wristbands for chemicals where observed urinary concentrations were relatively low as compared to background concentrations in the general population. Our findings support the growing body of research in support of deploying silicone wristbands as an important exposure assessment tool.
... Based upon the volume of breastmilk that an infant consumes per day it has been estimated that a breastfeeding infant can consume 1000-2000 ng of TCS daily 24,26 . In addition, while breastmilk has an important influence on infant survival and health reducing disease risk and promoting aspects of postnatal development 27 , environmental toxicants can still be transferred from the nurturing mother to newborns through lactation 28 . The constant presence of TCS in breastmilk in different studies and the high incidence of pediatric NAFLD led us to hypothesize that the transfer of TCS from lactating mothers to newborns can lead to NAFLD in children. ...
Here we show that Triclosan (TCS), a high-volume antimicrobial additive that has been detected in human breastmilk, can be efficiently transferred by lactation to newborn mice, causing significant fatty liver (FL) during the suckling period. These findings are relevant since pediatric non-alcoholic fatty liver disease (NAFLD) is escalating in the United States, with a limited mechanistic understanding. Lactational delivery stimulated hepatosteatosis, triglyceride accumulation, endoplasmic reticulum (ER) stress, signs of inflammation, and liver fibrosis. De novo lipogenesis (DNL) induced by lactational TCS exposure is shown to be mediated in a PERK-eIF2α-ATF4-PPARα cascade. The administration of obeticholic acid (OCA), a potent FXR agonist, as well as activation of intestinal mucosal-regenerative gp130 signaling, led to reduced liver ATF4 expression, PPARα signaling, and DNL when neonates were exposed to TCS. It is yet to be investigated but mother to child transmission of TCS or similar toxicants may underlie the recent increases in pediatric NAFLD. Triclosan is an antimicrobial additive in consumer products that has been detected in human breast milk. Here the authors report that exposure of pregnant mice to triclosan leads to lactational exposure to newborns and the development of liver steatosis.
... In a representative sample of participants aged R6 years, TCS was detected in the urine of nearly 75% of participants in the 2003-2004 National Health and Nutrition Examination Survey (NHANES) (10). Triclosan has also been detected in human breast milk (11,12), plasma (13,14), urine (10), brain (15), liver (15), and adipose tissue (15), correlating with consumer use patterns of the antimicrobial (1,16). In several investigations, females tended to exhibit higher TCS concentrations than males, and the age group with the highest TCS levels tended to be in the 20s (7). ...
OBJECTIVE
To examine and further characterize the association between urinary levels of triclosan (TCS), a ubiquitous, putative endocrine disrupting chemical, and risk of infertility.
DESIGN
Retrospective cross-sectional study using Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES).
SETTING and SUBJECTS
U.S. female participants who completed the reproductive health questionnaire and provided urine for TCS level measurement for years 2013–2016.
INTERVENTION
None.
MAIN OUTCOME MEASURE
Rates of presumed infertility based upon participants’ affirmative response to survey question RHQ074 (“Have you ever attempted to become pregnant over a period of at least a year without becoming pregnant?”).
RESULTS
11.7% of the overall female and 12.5% of the eligible study population met criteria for presumed infertility. Creatinine adjusted urinary TCS levels were significantly higher among those meeting criteria for infertility compared to those who did not, p=0.032. On multivariable adjusted analyses, individuals with undetectable levels of urinary TCS were 35% less likely to meet criteria for infertility compared to those with detectable TCS levels, p=0.049. The magnitude of association between TCS levels and infertility was strongest when comparing the lowest and highest quartiles. The directionality and magnitude of the relationship between TCS levels and infertility was maintained on age-restricted and weighted analyses, however the associations did not retain statistical significance.
CONCLUSIONS
In a nationally representative sample of women in the U.S., an association between TCS exposure and inability to conceive over a period of one year is suggested by our analysis of NHANES data. The data infers a dose-response relationship.
... TCS is hydrophobic in nature and easily accumulates in various tissues such as adipose, liver, or brain tissues; moreover, it can penetrate through biological barriers (Dhillon et al., 2015;Geens et al., 2012;Wang et al., 2015). Many studies have shown that TCS can be found in blood, urine, and breast milk samples (Allmyr et al., 2008(Allmyr et al., , 2006Dayan, 2007;Kim et al., 2011a;Mortensen et al., 2014;Toms et al., 2011). In addition, it has been evidenced that TCS can cause genotoxic, hepatotoxic, immunotoxic, neurotoxic, and cardiotoxic effects and interfere with the reproductive function and development of organisms (Ashley-Martin et al., 2016;Du et al., 2018;Huang et al., 2020;Parenti et al., 2019;Szychowski et al., 2020Szychowski et al., , 2019Szychowski et al., , 2015. ...
Epidemiological studies have shown the presence of triclosan (TCS) in the brain due to its widespread use as an antibacterial ingredient. One of the confirmed mechanisms of its action is the interaction with the aryl hydrocarbon receptor (AhR). In nerve cells, sirtuins (Sirt1 and Sirt3) act as cellular sensors detecting energy availability and modulate metabolic processes. Moreover, it has been found that Sirt1 inhibits the activation of estrogen receptors, regulates the androgen receptor, and may interact with the AhR receptor. It is also known that Sirt3 stimulates the production of estradiol (E2) via the estradiol receptor β (Erβ). Therefore, the aim of the present study was to evaluate the effect of TCS alone or in combination with synthetic flavonoids on the production of neurosteroids such as progesterone (P4), testosterone (T), and E2 in primary neural cortical neurons in vitro. The contribution of Sirt1 and Sirt3 as well as AhR to these TCS-induced effects was investigated as well. The results of the experiments showed that both short and long exposure of neurons to TCS increased the expression of the Sirt1 and Sirt3 proteins in response to AhR stimulation. After an initial increase in the production of all tested neurosteroids, TCS acting for a longer time lowered their levels in the cells. This suggests that TCS activating AhR as well as Sirt1 and Sirt3 in short time intervals stimulates the levels of P4, T, and E2 in neurons, and then the amount of neurosteroids decreases despite the activation of AhR and the increase in the expression of the Sirt1 and Sirt3 proteins. The use of both the AhR agonist and antagonist prevented changes in the expression of Sirt1, Sirt3, and AhR and the production of P4, T, and E2, which confirmed that this receptor is a key in the mechanism of the TCS action.
... Based upon the volume of breastmilk that an infant consumes per day it has been estimated that a breastfeeding infant can consume 1000-2000 ng of TCS daily 24,26 . In addition, while breastmilk has an important influence on infant survival and health reducing disease risk and promoting aspects of postnatal development 27 , environmental toxicants can still be transferred from the nurturing mother to newborns through lactation 28 . The constant presence of TCS in breastmilk in different studies and the high incidence of pediatric NAFLD led us to hypothesize that the transfer of TCS from lactating mothers to newborns can lead to NAFLD in children. ...
Pediatric non-alcoholic fatty liver disease (NAFLD) is escalating in the United States, with a limited mechanistic understanding. Triclosan (TCS) is a high-volume antimicrobial additive that has been detected in human breastmilk and shown in adult mice to cause hepatosteatosis. To examine the effect of TCS presented to neonatal mice through lactation, we exposed pregnant females to TCS in their diet and evaluated its impact on nursing neonates. TCS is efficiently transferred by lactation to newborn mice, causing significant fatty liver (FL) during the suckling period. Lactational delivery stimulated hepatosteatosis, triglyceride accumulation, endoplasmic reticulum (ER) stress, inflammation, and liver fibrosis. These events were mirrored by inhibition of key metabolic regulators, FGF21 and AMPK. De novo lipogenesis (DNL) induced by lactational TCS exposure was blocked in mice deficient in hepatic ATF4 . In primary hepatocytes, siRNA specific inhibition of PERK, an ATF4 upstream activator and initiator of ER stress, blocked TCS induced DNL. Also, in the absence of PPARα, which targets regulation of ATF4, TCS induced triglyceride accumulation and the induction of DNL was blocked. The administration of obeticholic acid (OCA), a potent FXR agonist, as well as activation of intestinal mucosal-regenerative gp130 signaling, led to reduced liver ATF4 expression, PPARα signaling, and DNL when neonates were exposed to TCS. In summary, TCS exposure via lactation leads to early indicators of NAFLD development accompanied by hepatosteatosis that were mediated in a PERK-eIF2α-ATF4-PPARα cascade. These studies indicate that mother to child transmission of environmental toxicants such as TCS may underlie the recent increases in pediatric NAFLD.
... As it is obviously ubiquitous across the ecosystem, the effects of TCS on human health have attracted attention. Nowadays, TCS has also been detected in diverse human body fluids and tissues (e.g., urine, plasma, milk, and fingernail) (6)(7)(8)(9). Research in animals shows that TCS is suspected to be an endocrinedisrupting chemical (EDC) and may adversely affect male sperm quality. In vitro study by Kumar et al. (10) demonstrated that TCS disrupted intermediate steroidogenic cascade and depressed testosterone synthesis. ...
Triclosan (2,4,4′-trichloro-2′-hydroxy-diphenyl ether, TCS) is widely used in personal care and household products. It is ubiquitous across the ecosystem nowadays. Several in vitro and in vivo studies have suggested the possible adverse effects of TCS on male reproductive health. However, little research has been done on human beings, especially in eastern countries. To assess the effects of TCS exposure on male fecundity, we recruited couples who planned to conceive and went to the preconception care clinics for physical examination in Shanghai, China. TCS was quantified in male urine samples collected at enrollment. For this study, 443 couples were included in the cohort, and 74.7% of couples (n = 331) were prospectively followed 12 months later. The outcomes of interest included the pregnancy status of their wives and time to pregnancy. Elevated male urinary TCS concentrations were found to be associated with diminished fecundability (fecundability odds ratio (FOR) 0.77; 95% CI, 0.62–0.97). The risk of infertility significantly increased (OR = 1.6; 95% CI, 1–2.6) as TCS levels elevated. Besides, we divided TCS concentration into tertiles a priori, and there tended to be a dose-response pattern in both analyses. Our findings suggest that environmental exposure to TCS may have an adverse impact on male fecundity.
... Moreover, 86.161 μg/L of TCS was detected in influent from municipal sewage treatment plant in Savannah, United States (Kumar et al., 2010;Miller et al., 2008), and 533 ng/L to 774 ng/L in Shanghai, China (Zhou et al., 2009). More seriously, TCS has been found in human tissue and body fluids including liver, brain, blood, urine and breast milk (Allmyr et al., 2006;Dann and Hontela, 2011;Geens et al., 2012;Pullaguri et al., 2020). It was reported the highest detected concentration of TCS in human urine samples was found in China which was 1600 μg/g (Iyer et al., 2018). ...
Triclosan (TCS) is widely used in personal care products and has become a contaminant ubiquitously found in the aquatic environment. It is reported exposure to triclosan can cause serious toxic effects on aquatic animals. However, the molecular mechanisms about long-term exposure to TCS-induced reproductive toxicity are not well elucidated. In the present study, adult zebrafish were exposed to TCS (2, 20 and 200 μg/L) for 150 days, and then the reproductive capacity assessment, steroid hormone and VTG quantitative measurement, histopathology observation and RNA sequencing analysis were performed to investigate the effects of TCS on its reproduction. The results indicated that long-term exposure to TCS causes the regulation disorder of the endocrine system, resulting in a reduction of the number of normal germ cells, and ultimately a decrease in the hatching rate and survival rate of offspring. This study revealed the toxic effects and contributed to our deep understanding about the potential disease of TCS exposure in the aquatic environment.
... For this reason, TCS can be regarded as a POP, which can accumulate in the fat tissue of exposed organisms, and can also be transported in water bodies over great distances. This has been shown in a study demonstrating high levels of TCS in blood plasma (163 times more) and breast milk (12 times more) in pregnant women compared to unexposed individuals (Allmyr et al., 2006). Although the use of TCS has been phased out in several personal care products in developed countries, it is still found in South African consumer products, and therefore detected in surface waters (Amdany et al., 2014b;Madikizela et al., 2014). ...
Global surface waters are increasingly shown to be contaminated by anthropogenic chemical pollutants which, in turn exert potential lethal- and sub-lethal toxicity risks to the aquatic environment and humans. In particular, pollutants which are able to modulate endocrine system pathways, known as endocrine disrupting contaminants (EDCs) are of an emerging global concern. Treated wastewater discharge is a major contributing source of this pollution, with the recalcitrance and passage of various contaminants through wastewater treatment posing a risk to water security. This is highlighted as a critically important global challenge which need to be further addressed, especially for developing countries that are subjected to increased demands for clean water and sanitation services due to rapid population growth and urbanisation. Furthermore, routine monitoring and refinement of analytical methodologies for risk assessment are largely limited in the country, which points to the needed to assess the harmful impact of priority micro-pollutants in surface water systems. One of the aims of the present study was to assess the presence and fate of EDCs and other emerging contaminants (ECs) within a selection of South African wastewater treatment works (WWTWs) and associated environmental waters in order to refine the monitoring tools and methodology used for risk assessment approaches.
Endocrine-disrupting activities generated by in vitro steroid hormone receptor binding assays, namely the yeast (anti)estrogen screen (YES/YAES), highlighted the complexity when dealing with environmental samples containing a mixture of analytes. Even though notable reductions of estrogenicity by the WWTWs were measured, some remaining loads in effluent receiving river waters remained above risk-based trigger values, therefore potentially compromising human- and aquatic health. Estimation of the potential toxic masking by analytes with anti-estrogenic effect/activity highlighted further refinement that will be needed evaluating potential endocrine disrupting activity when applying bioassays for risk assessment. Both diurnal as well as seasonal variation in endocrine disrupting activities were recorded and discussed. Also, treated wastewater effluent served as a diluting medium to lower estrogenicity within recipient river waters at some study sites, and highlighted the contribution of alternative pollution sources that may significantly impact the quality of river systems.
Although EDCs are mostly assumed to be associated with steroid hormones, in the present study I conducted scoping studies at selected WWTWs and showed the extent of regularly-used pharmaceuticals & personal care products (PPCPs) and drugs of abuse (DOA) present within wastewater and surface waters - having variable degradation profiles during wastewater treatment. In particular, ECs which were highlighted as priority micro-pollutants, such as anti-epileptics, non-steroidal anti-inflammatory drugs (NSAIDs), opioids and anti-depressants showed moderate- to negative removal during wastewater treatment, even during advanced activated sludge treatment processes. Although all of these pollutants are known to undergo biological degradation, the present study recommended further refinement of current treatment processes to improve on the removal of such persistent ECs. The need to define the environmental impact of EC breakdown-products were also discussed, as their potential health risks are largely unknown.
The dissertation also showed the value of urban water profiling to report on the use and abuse of licit and illicit DOA within communities connected to sewer networks at two study sites. Several prescription and over-the-counter (OTC) medications were detected within wastewater originating from domestic sewage, in particular opioids, an anaesthetic and anti-depressant drug – all of which are reported to be abused in South Africa, although limited statistics exist. For illicit DOA, the loads of cocaine, 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, heroin and the new psychoactive substance (NPS) mephedrone confirmed their consumption within the communities connected to the WWTWs, which were enriched by including the detection of their metabolic breakdown products, as well as enantiomeric profiling of the chiral drugs.
The present study encapsulated the benefit of urban water profiling to address current- and emerging global challenges for environmental- and human sustainability. Incorporation of the research outputs from the current study during refinement of risk-based approaches in South Africa may greatly improve water reclamation and management strategies to ultimately safeguard this valuable commodity for driving community- and environmental resilience.
... For this reason, TCS can be regarded as a POP, which can accumulate in the fat tissue of exposed organisms, and can also be transported in water bodies over great distances. This has been shown in a study demonstrating high levels of TCS in the breast milk of pregnant Swedish women (Allmyr et al., 2006). The pollution of TCS in the environment can therefore be assessed in a similar way to the exposure of organochloride insecticides in environmental waters, such as DDT and endosulfan, which are also shown to accumulate in the fat tissue of both wildlife and humans. ...
... Several parabens, phenols, polychlorinated compounds and phthalates are known or suspected to have endocrine disrupting properties and have been used widely in food packaging, cosmetics, pharmaceuticals and building materials for nearly a century (Baird et al., 2010). Biomonitoring and epidemiological studies have shown widespread exposure to these specific EDCs in the general population, including pregnant women (Allmyr et al., 2006;Cantonwine et al., 2014;Casas et al., 2011;Fisher et al., 2021;Frederiksen et al., , 2011Gyllenhammar et al., 2012;Mendiola et al., 2010;Philippat et al., 2012Philippat et al., , 2014Philippat et al., , 2013Silva et al., 2004;White et al., 2011;Wolff et al., 2008;Ye et al., 2009). However, the toxicokinetics of these chemicals is complex and the degree to which these chemicals reach the unborn human fetus is currently largely unknown. ...
Objective
To examine whether selected endocrine disrupting chemicals were present in pregnant women and passed through the placental barrier to amniotic fluid, potentially exposing the developing fetus.
Methods
Paired samples of maternal serum, urine and amniotic fluid were concurrently collected (<1 h) from 200 pregnant women (age >18 years) with a singleton pregnancy and undergoing amniocentesis between gestational weeks 12 – 36. The concentration of six different parabens, seven phenols, 31 metabolites from 15 phthalate diesters and the polychlorinated substance triclocarban were analyzed by isotope diluted TurboFlow-liquid chromatography-tandem mass spectrometry.
Results
Concentrations of all included compounds were highest in maternal urine followed by serum, and lowest in amniotic fluid. Of the six parabens measured in amniotic fluid, methylparaben (MeP) and ethylparaben (EtP) were detectable most often (87% and 33% of the samples, respectively). Of the seven phenols measured, three (2,4-dichlorphenol, 2,5-dichlorphenol, 2-propylphenol) were detectable in the range of 14–21% of the amniotic fluid samples, at low concentrations (<0.12 ng/ml). Two secondary phthalates metabolites, mono-(2-carboxymethyl-hexyl) phthalate and mono-carboxy-iso-octyl phthalate were each present in ≤15% of the amniotic fluid samples at concentrations 2–5 times lower than in maternal serum and 20–100 times lower than in maternal urine. A modest statistically significant correlation between the levels of MeP and EtP was detected in paired maternal urine-amniotic fluid samples was detected (Spearman rMeP: 0.246; rEtP: 0.364). Likewise, the concentration of mono-ethyl phthalate (MEP) in paired maternal urine and amniotic fluid samples indicated a modest statistically significant correlation (Spearman rMEP: 0.264), driven by detectable levels of MEP in only 3% of the amniotic fluid samples.
Conclusions
In general, the included parabens, phenols and phthalates were effectively metabolized and excreted via the urine, which was the matrix that reflected the highest detectable levels. The detectable levels of several included parabens and phthalates in human amniotic fluid calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of individual and multiple endocrine disruptors in order to better assess the risk to the developing fetus.
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.
Triclocarban (TCC) is an emerging environmental contaminant, posing potential ecological risks. Displaying a high accumulation effect and 120-day half-life in the soil environment, the toxic effects of TCC to soil organisms have been widely reported. Previous studies have confirmed that TCC can induce the oxidative stress and changes in superoxide dismutase (SOD) and catalase (CAT) activities in earthworms, but the underlying mechanisms of oxidative stress and disorder in antioxidant enzyme activities induced by TCC have not yet been elucidated. Here, we explored the multiple response mechanisms of SOD and CAT under the regulation of oxidative stress induced by TCC. Results indicated that higher-dose (0-2.0 mg/L) TCC exposure triggered the overproduction of ROS in Eisenia foetida coelomocytes, causing oxidative damage and a decrease in cell viability that was response to ROS accumulation. The TCC-induced inhibition of intracellular SOD/CAT activity was found under the regulation of oxidative stress (SOD: 29.2 %; CAT: 18.5 %), and this effect was blunted by antioxidant melatonin. At the same time, the interaction between antioxidative enzymes and TCC driven by various forces (SOD: electrostatic interactions; CAT: van der Waals forces and hydrogen bonding) led to inhibited SOD activity (9.84 %) and enhanced CAT activity (17.5 %). Then, to elucidate the binding mode of TCC, we explored the changes in SOD and CAT structure (protein backbone and secondary structure), the microenvironment of aromatic amino acids, and aggregation behavior through multispectral techniques. Molecular docking results showed that TCC inhibited SOD activity in a substrate competitive manner and enhanced CAT activity by the stabilizing effects of TCC on the heme groups. Collectively, this study reveals the response mechanisms of SOD/CAT under the regulation of TCC-triggered oxidative stress and shed a new light on revealing the toxic pathways of exogenous pollutants on antioxidant-related proteins function.
As a ubiquitous environmental estrogen-disrupting chemical, triclosan (TCS) can induce severe osteotoxicity; however, the underlying molecular mechanisms remain uncertain. Herein, we evaluated the toxic effects of TCS on the development of cartilage and osteogenesis in 5-dpf zebrafish. Under TCS exposure from 62.5 to 250 μg/L, several osteodevelopmental malformations were observed, such as defect of craniofacial cartilage, pharyngeal arch cartilage dysplasia, and impairments on skeletal mineralization. Further, the morphology of mature chondrocytes became swollen and deformed, their number decreased, nucleus displacement occurred, and most immature chondrocytes were crowded at both ends of ceratobranchial. SEM observation of larval caudal fin revealed that, the layer of collagen fibers and the mineralized calcium nodules were significantly decreased, with the collagen fibers becoming shorter upon TCS exposure. The activity of bone-derived alkaline phosphatase significantly reduced, and marker functional genes related to cartilage and osteoblast development were abnormally expressed. RNA-seq and bioinformatics analysis indicated, that changes in marker genes intimately related to the negative regulation of miR-30c-5p overexpression targeted by TCS, and the up-regulation of miR-30c induced bone developmental defects by inhibiting the bone morphogenetic protein (BMP) signaling pathway. These findings were confirmed by artificially intervening the expression of miR-30c and using BMP pathway agonists in vivo. In sum, TCS induced osteototoxicity by targeting miR-30c up-regulation and interfering in the BMP signaling pathway. These findings enhance mechanistic understanding of TCS-induced spontaneous bone disorders and bone metastatic diseases. Further research is necessary to monitor chronic TCS-exposure levels in surrounding environments and develop relevant safety precautions based on TCS environmental risk.
Triclosan (TCS), a bactericide, has recently been identified as a pollutant that exhibits endocrine-disrupting chemical effects. Today, the investigation of TCS in biological, environmental and pneumocystis pneumonia (PCP) samples is of primary concern. The present study involves the development of a new sensor for the sensing and investigation of TCS based on carbon paste modified with tungsten oxide nanorods (WO3) and reduced graphene oxide (rGO) nanocomposite in 0.2M phosphate buffer solution (PB). The analysis of samples of fruits, vegetables, soil, and water contaminated with TCS pesticide was followed through the square wave voltammetry (SWV) technique in pH 9.2 PB. The applied potential on the fabricated sensor oxidizes TCS at considerably greater oxidation currents than the bare carbon paste electrode (CPE). The electrochemical performance of TCS was measured by cyclic voltammetry (CV) and SWV. Nanostructured WO3 produces well-resolved peaks and enhanced electrochemical current response when opted as a modifier in electrode-based sensors. Given this, we proposed the synthesis of one dimensional (1-D) WO3 nanostructure and utilized it to analyze TCS. SEM, XRD, TEM, and XPS analysis evaluated the crystallinity, morphology, and structural properties. The produced 1-D WO3 exhibits a monoclinic crystal structure with oxygen vacancies in the lattice. Electro-kinetic parameters such as temperature effect, heterogeneous rate constant, and other parameters such as scan rate, accumulation time, activation energy, pH, thermodynamic parameters, and the number of protons and electrons involved in the TCS electro-oxidation were studied.
We recently reported that exposure to triclosan (TCS), a broad-spectrum antibacterial agent, affects social behaviors in adult mice, however, the long-lasting effects of TCS exposure during early life on social behaviors are still elusive. The present study aimed to investigate the long-lasting impacts of adding TCS to the maternal drinking water during lactation on the social behaviors of adult mouse offspring and to explore the potential mechanism underlying these effects. The behavioral results showed that TCS exposure decreased body weight, increased depression-like behavior and decreased social dominance in both male and female offspring, as well as increased anxiety-like behavior and bedding preference in female offspring. In addition, enzyme-linked immunosorbent assay (ELISA) indicated that TCS exposure increased peripheral proinflammatory cytokine levels, altered serum oxytocin (OT) levels, and downregulated the expression of postsynaptic density protein 95 (PSD-95) in the hippocampus. Morphological analysis by transmission electron microscopy (TEM) demonstrated that exposure to TCS induced morphological changes to synapses and neurons in the hippocampus of offspring. These findings suggested that TCS exposure during lactation contributed to abnormal social behaviors accompanied by increased peripheral inflammation and altered hippocampal neuroplasticity, which provides a deeper understanding of the effects of TCS exposure during early life on brain function and behavioral phenotypes.
In recent decades there has been a dramatic increase in the incidence and prevalence of inflammatory bowel disease (IBD), a chronic inflammatory disease of the intestinal tissues and a major risk factor of developing colon cancer. While accumulating evidence supports that the rapid increase of IBD is mainly caused by exposure to environmental risk factors, the identities of the risk factors, as well as the mechanisms connecting environmental exposure with IBD, remain largely unknown. Triclosan (TCS) and triclocarban (TCC) are high-volume chemicals that are used as antimicrobial ingredients in consumer and industrial products. They are ubiquitous contaminants in the environment and are frequently detected in human populations. Recent studies showed that exposure to TCS/TCC, at human exposure-relevant doses, increases the severity of colitis and exacerbates colon tumorigenesis in mice, suggesting that they could be risk factors of IBD and associated diseases. The gut toxicities of these compounds require the presence of gut microbiota, since they fail to induce colonic inflammation in mice lacking the microbiota. Regarding the functional roles of the microbiota involved, gut commensal microbes and specific microbial β-glucuronidase (GUS) enzymes mediate colonic metabolism of TCS, leading to metabolic reactivation of TCS in the colon and contributing to its subsequent gut toxicity. Overall, these results support that these commonly used compounds could be environmental risk factors of IBD and associated diseases through gut microbiota-dependent mechanisms.
Triclosan (TCS) is an organic substance showing antibacterial action, which is commonly used in many branches of industry, including, among others, cosmetics, pharmaceuticals and the food industry. TCS may penetrate into living organisms and negatively affect the health of humans and animals. The majority of previous investigations on TCS biomonitoring in humans have been performed on urine, but currently, studies on hair samples are becoming increasingly important. The aim of this study was to evaluate TCS concentration levels in residents of Olsztyn, a city in northeastern Poland, using a liquid chromatography-mass spectrometry technique. The presence of TCS was observed in 96.7% of samples tested, with concentration levels from 37.9 pg/mg to 3386.5 pg/mg. The mean concentration level of TCS in the present study was 402.6 (±803.6) pg/mg, and the median value was 103.3 pg/mg. Although there were some differences in TCS concentration levels between males and females, humans of various ages and humans with colored and natural hair had no statistically significant differences in TCS concentration levels. The obtained results have clearly indicated that people living in northeastern Poland are exposed to TCS to a large degree, and hair analysis, despite some limitations, is a suitable method for TCS biomonitoring in humans.
This work studied the application of adsorption with activated carbons (ACs) and photodegradation to reduce the concentration of triclosan (TCS) in aqueous solutions. Concerning the adsorption, the ACs (Darco, Norit, and F400) were characterized in detail, and batch experiments were applied to elucidate the effect of pH on the equilibrium. The results showed that at pH = 7, the maximum adsorption capacity of TCS onto the ACs was obtained, which was 18.5 mg g − 1 for Darco, 16.0 for Norit, and 15.5 for F400. The Diffusional kinetic model allowed an adequate interpretation of the experimental data. The effective diffusivity varied and increased along with the amount of TCS adsorbed, from 1.06 to 1.68×10 − 8 cm ² s − 1 . In the case of photodegradation, the removal percentage of TCS and sulfate radicals were verified. It was possible to ensure that the triclosan molecule was sensitive to UV light of 254 nm since the removal was over 80% using UV light. The removal of TCS was increased in the presence of sulfate radicals. It was possible to identify 2,4-dichlorophenol as one of the photolytic degradation products of triclosan, and it does not represent an environmental hazard at low concentrations of triclosan in water. These results confirm that the wastewater treatment methods proposed are effective for removing TCS from water, reaching levels of concentration that do not constitute a risk to human health or environmental hazard. Both methods effectively eliminate the pollutant with relatively easy techniques to implement.
Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kg•day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS.
Triclosan (TCS) is a typical environmental pollutant, which seriously threatens the health of humans and organisms. A novel strategy of biochar/Ag3PO4/polyaniline (PANI) composite photocatalyst was synthesized by a facile chemical precipitation method to efficiently degrade TCS. XRD, Raman, ESR, etc. were used to reveal the effective associations among physiochemistry, photochemistry and photocatalytic properties of the composite. It was proved the synergistic effects of biochar (T-Bio) and PANI resulted in the decrease of Ag3PO4 particle size, the enhancement of adsorption, the improvement of light utilization, the increase of photogenerated carrier separation and the promotion of reactive species. The photocatalytic mechanism showed h⁺ was the main active species, O2⁻ and OH played minor roles. Under the irradiation of visible light, the optimal photocatalyst (1.0% T-Bio/AP/1.0% PANI) displayed excellent photocatalytic activity with the removal rate of 85.21% for TCS within 10 min, and the apparent rate constant K′ was 2.38 times of Ag3PO4. 11 main intermediates for TCS degradation were identified, and their toxicity was significantly reduced. The possible degradation pathways were proposed. This work is the first systematic study on the degradation behavior of TCS by Ag3PO4-based photocatalyst, and it provides a new approach to fabricate photocatalysts with synergistic effects and amazing photocatalytic activity by biochar.
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
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Screening av triclosan och vissa bromerade fenoliska ämnen i Sverige. [Screening of triclosan and some brominated, phenolic compounds in Sweden
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