Article

Triclosan in Plasma and Milk from Swedish Nursing Mothers and Their Exposure via Personal Care Products

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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.

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... 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. ...
... Some studies have elucidated the occurrence of TCS and/or TCC in a wide range of PCPs from China, South Africa, and USA, with special concern for human exposures through dermal contact (Liao and Kannan, 2014;Lu et al., 2018;Musee, 2018;Gao and Kannan, 2020). As a result, TCS and TCC have been detected in human samples such as blood (Allmyr et al., 2006(Allmyr et al., , 2008Pycke et al., 2014), breast milk (Allmyr et al., 2006;Toms et al., 2011;Kim et al., 2020), urine (Calafat et al., 2008;Asimakopoulos et al., 2014;Xue et al., 2015;Iyer et al., 2018), and nails (Shi et al., 2013). TCS and TCC are considered as endocrine disruptors and their acute and chronic toxicity has been addressed but not fully understood (Bedoux et al., 2012;Halden, 2014;Lee et al., 2019;Vimalkumar et al., 2019;Yun et al., 2020). ...
... Some studies have elucidated the occurrence of TCS and/or TCC in a wide range of PCPs from China, South Africa, and USA, with special concern for human exposures through dermal contact (Liao and Kannan, 2014;Lu et al., 2018;Musee, 2018;Gao and Kannan, 2020). As a result, TCS and TCC have been detected in human samples such as blood (Allmyr et al., 2006(Allmyr et al., , 2008Pycke et al., 2014), breast milk (Allmyr et al., 2006;Toms et al., 2011;Kim et al., 2020), urine (Calafat et al., 2008;Asimakopoulos et al., 2014;Xue et al., 2015;Iyer et al., 2018), and nails (Shi et al., 2013). TCS and TCC are considered as endocrine disruptors and their acute and chronic toxicity has been addressed but not fully understood (Bedoux et al., 2012;Halden, 2014;Lee et al., 2019;Vimalkumar et al., 2019;Yun et al., 2020). ...
Article
Contamination status, spatial variability, and exposure risk of triclosan (TCS) and triclocarban (TCC) in indoor dusts from different micro-environments were evaluated for the first time in Vietnam as well as in Southeast Asian region. TCS and TCC were measured in 89 dust samples collected from bedrooms, living rooms, and kitchens of private houses in four northern cities including Hanoi, Bac Ninh, Hung Yen, and Nam Dinh, by means of liquid chromatography–tandem mass spectrometry. Concentrations of TCS and TCC ranged from <5 to 1090 (median 33.2) and from <3 to 531 (median 19.3) ng g−1, respectively. Concentrations of TCS and TCC in the kitchen and bedroom dusts were markedly higher than levels found in the living room samples, probably due to their applications in kitchen utensils, household cleaning reagents, and personal care products. A strong positive correlation between TCS and TCC concentrations was detected in the whole dataset (R2 = 0.810, p < 0.001). For samples in which both TCS and TCC were quantified, TCS/TCC ratios ranged from 0.3 to 12 with a median value of 1.8, and did not show big differences between micro-environments. Human exposures to TCS and TCC through dust ingestion were estimated for various age groups with 95% CI daily intake doses ranging from (0.032–0.070) to (0.340–0.740) and from (0.017–0.033) to (0.175–0.345) ng kg-bw−1 d−1 for adults and infants respectively. Although our derived values were much lower than reference doses, more comprehensive risk assessment considering multiple exposure pathways of TCS and TCC is needed.
... 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. ...
... ingestion of a single dose of mouthwash by 10 healthy volunteers (5 of whom were regularly using triclosan-containing products), plasma concentrations peaked at 0:5-1:2 lM (as opposed to preexperiment median triclosan plasma baseline concentration of 5:5 nM) up to 3 h after exposure ). Many studies have found triclosan in human urine (Heffernan et al. 2015;Philippat et al. 2013;Provencher et al. 2014;Yin et al. 2016), blood (Allmyr et al. 2006(Allmyr et al. , 2008, breast milk (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Toms et al. 2011), and amniotic fluid (Philippat et al. 2013). Studies on triclosan as a disruptor of the androgen, estrogen, and thyroid hormone axes are inconclusive. ...
... ingestion of a single dose of mouthwash by 10 healthy volunteers (5 of whom were regularly using triclosan-containing products), plasma concentrations peaked at 0:5-1:2 lM (as opposed to preexperiment median triclosan plasma baseline concentration of 5:5 nM) up to 3 h after exposure ). Many studies have found triclosan in human urine (Heffernan et al. 2015;Philippat et al. 2013;Provencher et al. 2014;Yin et al. 2016), blood (Allmyr et al. 2006(Allmyr et al. , 2008, breast milk (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Toms et al. 2011), and amniotic fluid (Philippat et al. 2013). Studies on triclosan as a disruptor of the androgen, estrogen, and thyroid hormone axes are inconclusive. ...
Article
Background: Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly difficult due to lack of adequate toxicological tests. This difficulty is particularly problematic for cosmetic ingredients, because in vivo testing is now banned completely in the European Union. Objectives: The aim was to identify candidate preservatives as endocrine disruptors by in silico methods and to confirm endocrine receptors' activities through nuclear receptors in vitro. Methods: We screened preservatives listed in Annex V in the European Union Regulation on cosmetic products to predict their binding to nuclear receptors using the Endocrine Disruptome and VirtualToxLab™ version 5.8 in silico tools. Five candidate preservatives were further evaluated for androgen receptor (AR), estrogen receptor ( ER α ), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cell-based luciferase reporter assays in vitro in AR-EcoScreen, hER α -HeLa- 9903 , MDA-kb2, and GH3.TRE-Luc cell lines. Additionally, assays to test for false positives were used (nonspecific luciferase gene induction and luciferase inhibition). Results: Triclocarban had agonist activity on AR and ER α at 1 μ M and antagonist activity on GR at 5 μ M and TR at 1 μ M . Triclosan showed antagonist effects on AR, ER α , GR at 10 μ M and TR at 5 μ M , and bromochlorophene at 1 μ M (AR and TR) and at 10 μ M ( ER α and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC50) IC 50 = 2.4 μ M ], as for its substantial ER α agonist at > 5 μ M and TR antagonist activity at 10 μ M . Climbazole showed AR antagonist ( IC 50 = 13.6 μ M ), ER α agonist at > 10 μ M , and TR antagonist activity at 10 μ M . Discussion: These data support the concerns of regulatory authorities about the endocrine-disrupting potential of preservatives. These data also define the need to further determine their effects on the endocrine system and the need to reassess the risks they pose to human health and the environment. https://doi.org/10.1289/EHP6596.
... Studies shows that triclosan is relatively well absorbed through the skin in all tested species, Human's application of products containing triclosan is dependent on the formulation, applied dose, duration of exposure, type of skin and skin [10,11] revealed that triclosan concentrations were higher in both plasma and milks from the mothers who used personal care products containing triclosan than in the mothers who did not. The triclosan concentrations were significantly higher in the exposed group. ...
... It was revealed that triclosan containing toothpaste and mouthwashes are considered to be the main sources of the varying triclosan concentrations found in a large part of the population in Sweden [13] Infant's exposure to triclosan through breastfeeding can be considered as Oral exposure though indirect. Thus, their exposure to triclosan was related to the mothers' exposure and the concentrations indicated that infant exposure to triclosan via breast milk is much less than the dose in the mother [11]. ...
... Information about the known commercial uses of triclosan indicates that ingestion and dermal absorption are the most likely routes of exposure [8,9]. Previous reported findings showed (anti) androgenic effects of triclosan in male rats [10], abortion and decline in estrogen sulfotransferase activity in mice [11] and triclosan found in breast milk of humans [12][13][14]. American researchers published 2517 urine samples of volunteers, of which the concentration of TCS was about 2.4-3790 ng/mL. ...
Article
Full-text available
Triclosan (TCN) was evaluated for reproductive and developmental toxicity on male and female reproductive performance such as gonadal function, mating behaviour, conception, development of the conceptus and parturition. Wistar rats (10/sex/dose) were administered by oral gavage at the dose levels of 0, 25, 75 and 150 mg/kg bwt/day, prior to mating, during mating and post-mating periods (for males), during pregnancy and up to lactation day 13 (for females). The results showed that, no treatment related mortality or clinical signs. Body weight, food consumption, pre-coital time, gestation length, mating and fertility parameters, percentage of pre-and post-implantation losses, anogenital distance, anogenital ratio were not affected by the treatment. The male pups did not exhibit areola/nipple retention on postnatal day 13. Treatment resulted in significantly lower mean litter size, mean viable litter size and mean number of implantations at 150mg/kg bwt/day. The Thyroid Stimulating Hormone (TSH) and Thyroxine (T4) levels in adult rats and pups were not affected. External evaluation of pups as well as gross and microscopic examination of the reproductive organs of the parent animals revealed no adverse triclosan related changes. Considering the changes observed in the mean litter size, mean viable litter size, mean number of implantations and Day 4 surviva index at 150mg/ kg bwt/day, the No Observed Adverse Effect Level (NOAEL)" for reproductive toxicity is considered to be 75mg/kg Bwt/day.
... A large number of products ranging from a small soap to kitchenware and electrical appliance is coated with Triclosan. Triclosan exposure has become so common these days that it has not only shown its presence in environmental samples but has also been found in urine samples (Calafat et al. 2008), blood samples (Calafat et al. 2008) and even in breast milk (Allmyr et al. 2006) of human beings across the globe. ...
Article
Full-text available
The Triclosan, a phenolic compound, is an antibacterial and antifungal agent present in the consumer daily need products such as toothpaste, soaps, detergents, toys and surgical cleaning treatments. This phenolic compound is an antimicrobial agent but it also seeks potential adverse effect on the organism and environmental health. Bioaccumulation of triclosan causes high level fatal effect on the aquatic life and this passively effect the human health. The prolonged exposure to this compound can have carcinogenic effect. The major source of triclosan in the environment is the sewage waste. The triclosan present in the water damages the aquatic life. They get accumulated in the body of lower animals and gradually they enter the food chain and also the food web of higher plant and animal. And this way it affects the human and environment. In environment, triclosan can be degraded by microorganisms into different other compound which may include chlorophenols and dioxine. In this present work the ability to degrade triclosan by different microorganism isolated from sewage is being checked. Isolate AS1001 was found to be the efficient degrader of Triclosan and it was also observed that it degraded triclosan more efiiciently in form of immobilized cells.
... p0240 Few examples on the antimicrobial agents that are commonly used in developing the antimicrobial textile have targeting microorganisms' cell membrane as the point of inhibition. For instance, triclosan or 2,4,4-hydrophenyl trichloro-II ether possesses the antiseptic and disinfectant properties and it is a halogen-typed compound that contains phenol which is regularly used in toothpaste and cosmetics making (Allmyr et al., 2006). The action of triclosan is known to be broad-spectrum 52 Fundamentals of Natural Fibres and Textiles because it acts on Gram-negative and Gram-positive bacteria via lipid biosynthesis blocking mechanism to give adverse effect on microorganisms' bacterial cell membrane integrity. ...
Chapter
Cellulose-based textile fibres have rapidly evolved since their first invention. It is an important source of reference in textile industries due to their universality and compatibility. Over time, the transition from natural to man-made fibre involved extensive research developments. By virtue of the better development, modification of native cellulose is not foreign in textile industries and offers a slew of benefits. Nonetheless, inventions were meant to meet current needs. Such needs include aesthetically pleasing and high mechanical strength, with low production cost. Current trends are into technological advancement providing textiles with self-heating and self-cooling properties, embedded with electrical devices, as well as, but not limited to, antibacterial property. Man-made cellulose-based textile has more to offer in comparison to native cellulose. However, all these advancements are still limited with renewability and sustainability. Both industries and consumers are the drivers to possibilities in the developments of textile technology.
... As well-known metabolites of PCBs, hydroxylated polychlorinated biphenyls (OH-PCBs) and PCB sulfates are toxic to various organisms (Grimm et al., 2015;Subramanian et al., 2017). Hydroxylated-PCBs are prevalent across a range of environmental media, including air (Awad et al., 2016;Marek et al., 2017), water (Darling et al., 2004;Kuch et al., 2010;Ueno et al., 2007), sediments (Marek et al., 2013a;Sakiyama et al., 2007) and humans (Allmyr et al., 2006;Fängström et al., 2004;Fängström et al., 2005;Marek et al., 2013b;Nomiyama et al., 2009;Quinete et al., 2015;Zota et al., 2013). Toxicity of OH-PCBs is often greater than that of their parent congeners in humans. ...
Article
Methoxylated polychlorinated biphenyls (MeO-PCBs) are overlooked metabolites of PCBs. In general, they are more toxic to plants than their parent congeners. However, information on the fate of MeO-PCBs and the relationship between methoxylated, hydroxylated and sulfated metabolites of PCBs in plants is scarce. In this work, poplar plants (Populus deltoides × nigra, DN34) were hydroponically and separately exposed to 4’-methoxy-4-monochlorobiphenyl (4’-MeO-PCB 3) and 4’-PCB 3 sulfate for 10 days to investigate the uptake, translocation and metabolism of MeO-PCBs and the relationship between methoxy-PCBs, hydroxyl-PCBs and PCB sulfates within plants. Results showed that 4’-MeO-PCB 3 and 4’-PCB 3 sulfate were taken up by the roots of poplar plants and translocated from roots to shoots and leaves. 4’-OH-PCB 3 and 4’-PCB 3 sulfate were identified as the hydroxylated metabolite and sulfate metabolite of 4’-MeO-PCB 3 in poplar, respectively. In the backward reaction, 4’-OH-PCB 3 and 4’-MeO-PCB 3 were found as metabolites of 4’-PCB 3 sulfate. For exposure groups, the yields of 4’-OH-PCB 3 produced from 4’-MeO-PCB 3 and 4’-PCB 3 sulfate were 1.29% and 0.13% respectively. The yield of 4’-PCB 3 sulfate which originated from 4’-MeO-PCB 3 in wood and root samples of exposure groups was only 0.02%. Only 0.04% of the initial mass of 4’-PCB 3 sulfate was transformed to 4’-MeO-PCB 3 in the exposure groups. The sulfation yield of 4’-OH-PCB 3 was higher than hydrolysis yield of 4’-PCB 3 sulfate, indicating that formation of PCB sulfates was predominant over the reverse reaction, the formation of hydroxy-PCBs. These results provide new perspective on the transport, metabolism, and fate of MeO-PCBs, and also help to better understand sources of OH-PCBs and PCB sulfates in the environment. This study provides the first evidence of interconversion of sulfate metabolites from methoxy-PCBs and methoxy-PCBs from PCB sulfates.
... Concentrations were shown to be higher in both plasma and milk from mothers who used personal care products containing triclosan than from mothers who did not. It has been shown that personal care products containing triclosan were one of the dominant sources of exposure to triclosan [5]. ...
Article
Full-text available
We present a densitometric quantification method for triclosan in toothpaste, separated by high-performance thin-layer chromatography (HPTLC) and using a 48-bit flatbed scanner as the detection system. The sample was band-wise applied to HPTLC plates (10 × 20 cm), with fluorescent dye, Merck, Germany (1.05554). The plates were developed in a vertical developing chamber with 20 min of chamber saturation over 70 mm, using n -heptane–methyl tert -butyl ether–acetic acid (92:8:0.1, V/V ) as solvent. The R F value of triclosan is hR F = 22.4, and quantification is based on direct measurements using an inexpensive 48-bit flatbed scanner for color measurements (in red, green, and blue) after plate staining with 2,6-dichloroquinone-4-chloroimide ( Gibbs' reagent). Evaluation of the red channel makes the measurements of triclosan very specific. For linearization, an extended Kubelka–Munk expression was used for data transformation. The range of linearity covers more than two orders of magnitude and is between 91 and 1000 ng. The separation method is inexpensive, fast and reliable.
... However, our understanding about the molecular targets and mechanisms of triclosan induced neurotoxicity in developing vertebrates is still limited especially when the exposures are for prolonged durations and at sublethal concentrations. This is important as triclosan has already been reported to be bioaccumulated in various human tissues and fluids including brain (Allmyr et al., 2006;Calafat et al., 2007;Fang et al., 2010;Geens et al., 2012). In this study, we hypothesized that sublethal triclosan concentrations are potent enough to alter motor neuron structure and function. ...
Article
The widespread use of triclosan in personal care products as an antimicrobial agent is leading to its alarming tissue-bioaccumulation including human brain. However, knowledge of its potential effects on the vertebrate nervous system is still limited. Here, we hypothesized that sublethal triclosan concentrations are potent enough to alter motor neuron structure and function in zebrafish embryos exposed for prolonged duration. In this study, zebrafish embryos were used as vertebrate-animal model. Prolonged exposure (up to 4 days) of 0.6 mg/L (LC50, 96 h) and 0.3 mg/L (<LC50, Sublethal) triclosan produced aberrations in motor neuron innervations in skeletal muscles and reduced touch-evoked escape response in zebrafish larvae. This suggests motor dysfunction in treated embryos. To further explore the mechanisms of triclosan induced neurotoxicity, we determined the enzyme activity of acetylcholinesterase (AChE) and the expression of acetylcholinesterase (ache), myelin basic protein (mbp) and synapsin IIa (syn2a) genes which play an important role in the neural development and synaptic transmission. The ache and syn2a genes were down-regulated in triclosan treated larvae without any significant changes in mbp gene expression. At functional level, we observed a decrease in the AChE activity. Furthermore, docking results showed that triclosan can form a stable interaction with binding pocket of AChE and perhaps it can compete with natural acetylcholine for direct binding to AChE thereby inhibiting it and affecting cholinergic transmission. Therefore, triclosan can be regarded as a neurotoxic agent even at sublethal concentrations. Overall, the growing toxicological evidence against triclosan including ours suggest caution in its widespread use.
... Along with it, aromatic nature and high chlorine content have been related to its lower degradation and higher persistence in the environment (Yueh and Tukey 2016). Its persistence in surface water and aerobic soils has been reported to be about 18 days (Bester 2005;Ying and Kookana 2007;Jimoh and Sogbanmu 2021), and its high levels have been recorded in algae, crustaceans, shellfish, fishes, marine mammals and urine, blood, liver, adipose tissue, brain and breast milk of humans (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Heffernan et al. 2015;Iyer et al. 2018). TCS is highly toxic to the organisms living in the aquatic environment particularly immediately downstream of the effluents from household wastewaters (Brausch and Rand 2011). ...
Article
Full-text available
Triclosan (TCS) used commonly in pharmaceuticals and personal care products has become the most common pollutant in water. Three-day-old hatchlings of an indigenous fish, Labeo rohita, were given 96h exposure to a nonlethal (60 μg L−1) and two moderately lethal concentrations (67 and 97 μg L−1) of TCS and kept for 10 days of recovery for recording transcriptomic alterations in antioxidant/detoxification (SOD, GST, CAT, GPx, GR, CYP1a and CYP3a), metabolic (LDH, ALT and AST) and neurological (AchE) genes and DNA damage. The data were subjected to principal component analysis (PCA) for obtaining biomarkers for the toxicity of TCS. Hatchlings were highly sensitive to TCS (96h LC50 = 126 μg L−1 and risk quotient = 40.95), 96h exposure caused significant induction of CYP3a, AChE and ALT but suppression of all other genes. However, expression of all the genes increased significantly (except for a significant decline in ALT) after recovery. Concentration-dependent increase was also observed in DNA damage [Tail Length (TL), Tail Moment (TM), Olive Tail Moment (OTM) and Percent Tail DNA (TDNA)] after 96 h. The damage declined significantly over 96h values at 60 and 67 μg L−1 after recovery, but was still several times more than control. TCS elicited genomic alterations resulted in 5–11% mortality of exposed hatchlings during the recovery period. It is evident that hatchlings of L. rohita are a potential model and PCA shows that OTM, TL, TM, TDNA, SOD and GR (association with PC1 during exposure and recovery) are the biomarkers for the toxicity of TCS. Graphical abstract
... In vitro, TCS has been also shown to be a potent inhibitor of enzymes which are responsible for the detoxification of multiple industrial chemicals by blocking the genetic transcription of several key human liver enzymes. These enzymes are responsible for the "biotransformation of steroids, pharmaceuticals and other xenobiotics" [38,72,153]. TCS has also been shown to cause significant oxidative stress to the human liver and there are concerns about its hepatocarcinogenic potential [154]. ...
Article
Full-text available
Antimicrobial compounds are used in a broad range of personal care, consumer and healthcare products and are frequently encountered in modern life. The use of these compounds is being reexamined as their safety, effectiveness and necessity are increasingly being questioned by regulators and consumers alike. Wastewater often contains significant amounts of these chemicals, much of which ends up being released into the environment as existing wastewater and sludge treatment processes are simply not designed to treat many of these contaminants. Furthermore, many biotic and abiotic processes during wastewater treatment can generate significant quantities of potentially toxic and persistent antimicrobial metabolites and byproducts, many of which may be even more concerning than their parent antimicrobials. This review article explores the occurrence and fate of two of the most common legacy antimicrobials, triclosan and triclocarban, their metabolites/byproducts during wastewater and sludge treatment and their potential impacts on the environment. This article also explores the fate and transformation of emerging alternative antimicrobials and addresses some of the growing concerns regarding these compounds. This is becoming increasingly important as consumers and regulators alike shift away from legacy antimicrobials to alternative chemicals which may have similar environmental and human health concerns.
... Due to incomplete elimination (72%e93%) by conventional treatment technologies, a considerable portion of triclosan in wastewater survives treatment and is unavoidably discharged into water bodies (Kookana et al., 2011). Therefore, triclosan has been detected in wastewater treatment plant effluents, natural waters (Bock et al., 2010;Cantwell et al., 2010;Fu et al., 2016) and various organisms including algae, fish and humans (Allmyr et al., 2006;Dayan, 2007;Oliveira et al., 2009). For instance, triclosan in a concentration range of 1e10 mg/L was detected in wastewater treatment plant effluent (Adolfsson-Erici et al., 2002;Ying et al., 2007). ...
Article
Triclosan (TCS) has attracted increasing concern due to its ubiquitous occurrence in aquatic environments as well as its potential adverse effects on human health. This study investigated the toxicity and transformation characteristics of triclosan ozonation and chlorination. The results showed that two hydroxylated by-products were formed via nucleophilic substitution during ozonation, while three chlorinated compounds were generated via electrophilic substitution during chlorination. The toxicity results demonstrated that the parent compound, triclosan, exhibited mild genotoxicity and anti-estrogenic activity. The chlorination of triclosan resulted in a 30-fold increase in anti-estrogenic activity owing to the generation of toxic polychlorinated transformation by-products. In addition, the chlorination by-products were found to be genotoxic like the parent compound. Fortunately, in contrast to chlorination, ozonation could mitigate the genotoxicity and anti-estrogenic activity of triclosan-containing water.
... Continuous use of personal care products (especially oral products) and accidental consumption of TCS contaminated water or fish may have led to its presence in tissues (adipose, brain, liver and nails) and body fluids of human beings (Allmyr et al., 2006;Geens et al., 2012;Toms et al., 2011). TCS has been reported to cause skin allergy (Bertelsen et al., 2013), disruption of thyroid function (Axelstad et al., 2013), impairment of muscle contraction (Cherednichenko et al., 2012), alteration of estrogen activity (Gee et al., 2008), reduction in testosterone synthesis and sperm count (Kumar et al., 2009) and significant elevation of B-cells, T-cells, dendritic cells and NK cells (Anderson et al., 2016) in humans. ...
Article
In the current study, Triclosan (TCS, a commonly used antimicrobial agent) induced alterations in biochemical parameters and gene expression were recorded in the larvae of Labeo rohita after 96 h exposure and 10 days recovery period to find out health status biomarkers. 96 h exposure to 0.06, 0.067 and 0.097 mg/L TCS significantly declined the levels of glucose, triglycerides, urea and uric acid and activity of alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). There was a non-significant decline in the levels of cholesterol and total protein but albumin and total bilirubin showed no change. After 10 days of recovery period, trend was opposite for glucose, urea and ALP only. Decline in the expression of trypsin and pancreatic amylase and elevation in creatine kinase during exposure to TCS showed a reverse trend after recovery period. However, concentration dependent elevation of chymotrypsin persisted till the end of recovery period. Principal Component Analysis (PCA) showed association of total protein, ALP, GOT, creatine kinase and pancreatic amylase with PC1 after exposure as well as recovery period. Therefore, these can be considered as important biomolecules for identification of health status of TCS stressed fish.
... Although the wastewater treatment process can lead to apparent triclosan removal efficiency [18][19][20][21], residues of the order of the traces persist in effluents and can be detected in receiving waters and aquatic environments. Although the adverse impact on human health is not fully understood, triclosan has been reported to be a likely endocrine disruptor [22,23], disrupting homeostasis of thyroid hormone [24] and estrogen-dependent responses [25]. ...
Article
In this work, Simple Walled Carbon Nanotubes (SWCNTs) were used as adsorbents to remove triclosan (TCS) from aqueous solution. The material characterization consisted of SEM/EDS and TEM/EDS analysis, surface characterization, and the determination of the pH at the point of zero charge. The effect of solution pH on the adsorption equilibrium was investigated in batch experiments. The overall adsorption rate of TCS on SWCNTs was investigated by applying kinetic models and a diffusional model based on pore volume diffusion. The results showed that a maximum adsorption capacity of TCS onto SWCNTs is obtained at a pH value of 7, which is 30.3 mg g⁻¹. The adsorption kinetics of TCS on SWCNTs was interpreted correctly by the First Order Kinetic Model and the Diffusional Model. The values of Dep varied from 1.06 to 1.20×10⁻⁸ cm² s⁻¹ and increased discretely as the mass of TCS adsorbed at equilibrium increased.
... Environmental exposure to triclosan may occur via consumer products that contain TCS, but also through water and/or food products contaminated with TCS (Weatherly and Gosse 2017). Detectable levels of TCS were found in milk and blood of nursing mothers (0.25-2.1 μg/L) (Allmyr et al. 2006) and human urine (2.4-3.7 μg/L) (Calafat et al. 2008). After oral exposure, urinary excretion increases in humans within 24 h. ...
Article
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Triclosan (TCS) is a widespread environmental endocrine-disrupting chemical. Animal and in vitro studies suggested that triclosan may affect homesostasis of sex and thyroid hormones and impact on reproduction. Due to limited data derived from human epidemiological studies, this study was performed to examine the association between urinary concentration of triclosan and in vitro reproductive outcomes (methaphase II (MII) oocyte yield, top quality embryo, fertilization rate, implantation rate, and clinical pregnancy) among women from infertility clinic. The study participants were enrolled in an Infertility Center in Poland. A total of 450 women aged 25-45 (n = 674 IVF cycles) provided urine samples. The urinary concentrations of triclosan were evaluated using validated gas chromatography ion-tap mass spectrometry method. Clinical outcomes of IVF treatment were abstracted from patients electronic chart records. Triclosan was detected in urine of 82% of women with geometric mean 2.56 ± 6.13 ng/mL. Urinary concentrations of triclosan were associated with decrease implantation rate (p = 0.03). There were no association between other examined IVF outcomes: MII oocytes, embryo quality, fertilization rate, and exposure to triclosan. As this is one of the first study on this topic, studies among larger and more diverse population are needed to confirm the results.
... Moreover, this substance is used in medicine as an ingredient of wound disinfectants and hand cleaners (Giuliano and Rybak, 2015). TCS can be detected in many human body fluids such as breast milk or urine and blood samples (Allmyr et al., 2006(Allmyr et al., , 2008Dayan, 2007;Kim et al., 2011;Mortensen et al., 2014;Toms et al., 2011). TCS is a non-volatile lipophilic compound with the ability to accumulate in various tissues such as liver, brain, and adipose tissue (Dhillon et al., 2015;Geens et al., 2012;Wang et al., 2015). ...
Article
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Triclosan (TCS) is a well-known compound that can be found in disinfectants, personal care products. There is one publication concerning the involvement of PPARγ in the mechanism of action of TCS. It is known that activation of PPARγ regulates the expression of the NF-κB mediated inflammation by acting on nitric oxide synthase (NOS) genes. However, there are no studies demonstrating a relationship between the effects of TCS on the PPARγ signaling pathway, changes in NF-κB expression, and NOS isoform synthesis. Therefore, the aim of this study was to evaluate the effect of TCS on the expression of PPARγ, NF-κB, nNOS, iNOS, and eNOS in mouse neocortical neurons. In addition, the effects of co-administration of synthetic alpha-naphthoflavone (αNF) or beta-naphthoflavone (βNF) flavonoids and triclosan were investigated. Our results show that TCS alters PPARγ, NF-κB, iNOS, and eNOS expression in mouse neurons in vitro. After 48 h of exposure, TCS increased PPARγ expression and decreased NF-κB expression. Moreover, under the influence of TCS, the expression of iNOS was increased and at the same time the expression of nNOS was decreased, which was probably caused by high levels of ROS. The experiments have shown that both αNF and βNF are able to modulate the effects of TCS in primary cultures of mouse cortical neurons.
... TCS is metabolized to glucuronide and sulfate conjugates (phase II metabolism) and primarily excreted by urine [6] . As a result of metabolism, it passes to body fluids, breast milk, and urine [7,8] and then merges into sewerage system via wastes, which causes wide contamination in the environment, such as in drinking water and surface waters [1,9] . Therefore, people using TCS-containing products are directly at risk and individuals drinking water contaminated with TCS are indirectly at risk. ...
Article
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Triclosan (TCS) is a broad spectrum antimicrobial agent showing its effect by deactivating the fatty acid synthesis of bacteria. The aim of this study was to investigate the effects of TCS on in vitro embryonic development in rats and to determine the levels of caspases 2, 7, 8, and 9 inducing cells to apoptosis through gene expression. According to the TCS dose added to the culture whole rat serum, 3 experimental groups and a control group were formed with each including 10 embryos. After 48 h culturing period, embryos were subjected to morphological scoring for developmental evaluation. The levels of caspases 2, 7, 8, and 9 were measured by performing gene expression on 40 embryos. Significant decreases were obtained in all parameters of morphological scoring in the experimental groups as the dose of TCS increased. While the caspase-2 level showed a significant decrease among the groups and was inversely proportional to the level of TCS, the caspase-9 level showed a significant increase among the groups and was directly proportional to the level of TCS. In conclusion, TCS was determined to cause apoptosis in the cells via the intrinsic pathway during pregnancy period and lead to embryonic growth retardation, which increased with increased dose of TCS.
... 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. ...
Article
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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.
... Many papers have shown that TCS can be absorbed by the gastrointestinal tract and the skin of human and animals (Rodricks et al., 2010). A number of studies have revealed the presence of TCS in human tissues, such as fat, liver, and brain, in addition to blood and breast milk (Allmyr et al., 2006;Geens et al., 2012;Toms et al., 2011;Wang et al., 2015). Moreover, significant concentrations of TCS have been detected in the brain of fish (13-88 ng/g ≈ 47.14-319.12 ...
Article
Triclosan (TCS) is commonly used worldwide in a range of personal care and sanitizing products. A number of studies have revealed the presence of TCS in human tissues. It has recently been shown that TCS can interact with AhR in mouse neurons and the one of its effects is the stimulation of reactive oxygen species (ROS) production. Reactive oxygen species perform a wide spectrum of functions in neuronal cells, where they are generated as by-products of cellular metabolism. Therefore the aim of the study was to investigate effects of two synthetic naphthoflavones, the beta-naphthoflavone (βNF) and alpha-naphthoflavone (αNF), well known agonist and antagonist of AhR on TCS-stimulated cytotoxicity, apoptosis and ROS production in mouse primary cortical neurons in vitro cultures. The results showed that both agonist (βNF) and antagonist (αNF) of AhR enhanced the LDH release and caspase-3 activity stimulated by TCS. Interestingly, both naphthoflavones decreased the TCS-stimulated ROS production, however, they showed no scavenging properties as revealed by ABTS•+ and DPPH• methods. What's more, both βNF as well as αNF inhibited the activity of xanthine oxidase (XO) stimulated by TCS. Thus, we can assume that αNF or βNF act in a competitive way over TCS and inhibit its effect on antioxidant enzyme activity.
... 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. ...
Article
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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.
... The presence of TCS in the breast milk of Swedish women was first reported by [23]. [41] also revealed the measurable levels of TCS in milk and blood of nursing mothers. [42] correlated the urinary TCS concentrations increased allergies diagnoses in the under 18 age group. ...
... Along with it, aromatic nature and high chlorine content have been related to its lower degradation and higher persistence in the environment (Yueh and Tukey 2016). Its persistence in surface water and aerobic soils has been reported to be about 18 days (Bester 2005;Ying and Kookana 2007) and its high levels have been recorded in algae, crustaceans, shell sh, shes, marine mammals and urine, blood, liver, adipose tissue, brain and breast milk of humans (Adolfsson-Erici et al. 2002;Allmyr et al. 2006;Heffernan et al. 2015). TCS is highly toxic to the organisms living in the aquatic environment particularly immediately downstream of the e uents from household wastewaters (Brausch and Rand 2011). ...
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Triclosan (TCS) used commonly in pharmaceuticals and personal care products has become the most common pollutant in water. Three days old hatchlings of an indegenous fish, Labeo rohita were given 96h exposure to an environmentally relevant (0.06mg/L) and two moderately lethal concentrations (0.067 and 0.097 mg/L) of TCS and kept for 10 days of recovery for recording transcriptomic alterations in antioxidant/detoxification (SOD, GST, CAT, GPx, GR, CYP1a and CYP3a), metabolic (LDH, ALT and AST) and neurological (AchE) genes and DNA damage. The data were subjected to Principal Component Analysis (PCA) for obtaining biomarkers for the toxicity of TCS. Hatchlings were highly sensitive to TCS (96h LC 50 = 0.126mg/L and risk quotient = 40.95), 96h exposure caused significant induction of CYP3a, AChE and ALT but suppression of all other genes. However, expression of all the genes increased significantly (except for a significant decline in ALT) after recovery. Concentration dependent increase was also observed in DNA damage [Tail Length (TL), Tail Moment (TM), Olive Tail Moment (OTM) and Percent Tail DNA (TDNA)] after 96h. The damage declined significantly over 96h values at 0.06 and 0.067 mg/L after recovery, but was still several times more than control. TCS elicited genomic alterations resulted in 5-11% mortality of exposed hatchlings during the recovery period. It is evident that hatchlings of L. rohita are a potential model and PCA shows that OTM, TL, TM, TDNA, SOD and GR (association with PC1 during exposure and recovery) are the biomarkers for the toxicity of TCS.
... 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). ...
Thesis
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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. ...
Article
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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.
... Indeed, the aromatic nature of TCS and its high chlorine content make it resistant to degradation and persistent in the environment (16). In humans, TCS has been detected in urine samples from pregnant women (17) and in maternal plasma and breastmilk (18). It is also known that TCS crosses the placenta (19). ...
Article
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Triclosan (TCS) is a phenolic compound with broad-spectrum antimicrobial action that has been incorporated into a variety of personal care products and other industry segments such as toys, textiles, and plastics. Due to its widespread use, TCS and its derivatives have been detected in several environmental compartments, with potential bioaccumulation and persistence. Indeed, some studies have demonstrated that TCS may act as a potential endocrine disruptor for the reproductive system. In the current study, we are reporting on the results obtained for male rats after a two-generation reproduction toxicity study conducted with TCS. Female and male Wistar rats were treated daily by gavage with TCS at doses of 0.8, 2.4, and 8.0 mg/kg/day or corn oil (control group) over 10 weeks (F0) and over 14 weeks (F1) before mating and then throughout mating, until weaning F2 generations, respectively. TCS exposure decreased sperm viability and motility of F1 rats at the dose of 2.4 mg/kg. The effects of TCS on sperm quality may be related to the exposure window, which includes the programming of reproductive cells that occurs during fetal/neonatal development.
Chapter
The ‘developmental origins of health and disease’ (DOHaD) suggests that early-life stress can affect the risk of later-onset diseases, while the potential mechanisms remain largely unknown. Epigenetics is defined as changes in gene expression that occur without changes in DNA sequence and can be transmitted to offspring. Increasing evidence has suggested that epigenetic regulation might be involved in developmental programming of late-onset pathologies. Here, we review current understandings of the relationship between early-life exposure of several endocrine-disrupting chemicals (EDCs) and later-life diseases, as well as potential epigenetic mechanisms.
Article
Triclosan (TCS) is widely used as an antibacterial agent, but its residue in the environment poses a great threat. In this study, Drosophila melanogaster were treated with series concentrations of TCS and the effects on development, behavior, reproduction, and oxidative stress indicators were investigated. The results showed that that high concentrations of TCS severely interfered with the metamorphosis, resulting in lower hatching rate and longer development time. The hatching rate was only 75.00% ± 4.08% in 0.80 mg/mL TCS group. TCS also showed dose-dependent damage to the fertility of flies, causing ovarian defects and decreased the number of offspring. Almost no offspring adults hatched when exposed to high concentrations of TCS (0.50 and 0.80 mg/mL), and the hatching rate was 0% in 0.80 mg/mL TCS group. Larvae crawling, adult climbing and anti-starvation ability were also affected to varying degrees and showed hormesis. TCS could damage larval intestinal cells in a dose-dependent manner, and injury was lightened with culture time prolonging to 30 h. It is noteworthy that TCS caused redox imbalance with an increase on catalase (CAT) activity and decrease on reactive oxygen species (ROS) level. Our results conclude that TCS elicits multiple impacts on Drosophila and its rational use should be strengthened.
Article
Triclosan (TCS) is widely used in personal hygiene products, such as mouthwash and toothpaste, and is found in human tissues. Interleukin (IL)-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) are pro-inflammatory cytokines and inappropriately elevated levels of each have been associated with pathologies including rheumatoid arthritis and certain cancers. Here we examine effects of TCS on the secretion of the pro-inflammatory cytokines from human immune cell preparations. TCS at concentrations between 0.05-5 µM consistently increased the secretion of IL-1β, IL-6, and TNFα within 24 h of exposure and the increases often maintained out to 6 days of exposure. TCS also induced increases in IFNγ secretion, however the increases were most consistent after 48 h of exposure rather than within 24 h. Additionally, a role for both p44/42 and p38 MAPK in TCS-stimulated increases in IL-1β was seen in cells from some donors.
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Phthalates and phenols are readily detected in human breast milk, but the contribution of breast milk feeding to an infant’s exposure to these chemicals is unknown. Among 248 mother-infant pairs in the HOME Study, we assessed breast milk consumption via maternal report and quantified concentrations of eight phthalate metabolites and three phenols (bisphenol A, triclosan, benzophenone-3) in infants’ urine at age 12 months. We estimated covariate-adjusted percent differences in phthalate metabolite and phenol concentrations by breast milk consumption. Seventy infants (28%) were fed some breast milk up to age 12 months. Urinary phenol concentrations were similar in infants who were or were not fed breast milk at 12 months. In contrast, urinary concentrations of monocarboxyisooctyl phthalate (MCOP) and mono-3-carboxypropyl phthalate (MCPP) were 42% (95% CI:3,97) and 24% (95% CI:-8,62) higher among infants fed breast milk at 12 months, respectively. Moreover, MCOP and MCPP concentrations were positively associated with the quantity of breast milk consumed in the prior month and 24 hours. In this cohort, we found evidence suggesting that breast milk consumption may be a source of exposure to some phthalates. Future studies should examine whether plastic feeding bottles or pumped milk is a potential exposure source among infants.
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Extensive use of triclosan (2,4,4′‐trichloro‐2′‐hydroxydiphenyl ether) as an antimicrobial agent in household and personal care products has resulted in global exposure of the human population. Its presence in human tissues, including milk, and its oestrogen‐disrupting properties raise concerns for an involvement in breast cancer. Because metastatic tumour spread is the main cause of breast cancer mortality, we have investigated the effects of triclosan on cell migration and invasion using three human breast epithelial cell lines and using concentrations comparable with those in human tissues. Long‐term exposure to 10⁻⁷ M of triclosan resulted in increased migration and invasion as measured by xCELLigence technology for all three cell lines, for the immortalized but nontransformed MCF‐10F breast epithelial cells (after 28 weeks), the oestrogen‐responsive MCF‐7 breast cancer cells (after 17 weeks) and the oestrogen‐unresponsive MDA‐MB‐231 breast cancer cells (after 20 weeks). The effects were therefore not limited to cancerous cells or to oestrogen‐responsive cells. This was paralleled in the MCF‐10F and MCF‐7 (but not MDA‐MB‐231) cells by a reduction in levels of E‐cadherin mRNA as measured by reverse transcription–polymerase chain reaction (RT‐PCR) and of E‐cadherin protein as measured by western immunoblotting, suggesting a mechanism involving epithelial‐to‐mesenchymal transition. This adds triclosan to the increasing list of ingredients of personal care products that can not only enter human breast tissue and increase cell proliferation but also influence cell motility. If mixtures of components in household and personal care products contribute to increasing cell migration and invasion, then reduction in exposure could offer a strategy for reducing breast cancer spread.
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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.
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Human activity is responsible for producing several chemical compounds, which contaminate the aquatic environment and adversely influence the survival of aquatic species and indirectly human health. Triclocarban (TCC) belongs to the category of emerging pollutants and its presence in aquatic environment is justified by its wide use as antimicrobial agent in personal care products. The concern about this chemical is due to the risk of persistence in water and soils and bioaccumulation, which contributes to human exposition through the contaminated food consumption. The present study evaluated the developmental toxicity of TCC in zebrafish early-life stages starting with the assessment of acute toxicity and then focusing on the integrative analyses of the observed phenotype on zebrafish development. For this purpose, lethal and sublethal alterations of zebrafish embryos were investigated by the Fish Embryo Acute Toxicity Tests (FET tests). Subsequently, two concentrations of TCC were used to investigate the morphometric features and defects in larvae developmental pigmentation: an environmentally relevant (5μg/L) and toxicological (50μg/L), derived from the No Observed Effect Concentration (NOEC) value concentration. Furthermore, the expression levels of a key transcription factor for melanocyte differentiation and melanin syntheses, such as mitfa (microphthalmia-associated transcription factor) and tyr (tyrosinase) and its activity, were evaluated.
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Triclosan (TCS) is widely applied in personal care products (PCPs) as an antimicrobial preservative. Due to its toxicity and potential risk to human health, TCS has attracted mounting concerns in recent years. However, biomonitoring of TCS in large human populations remains limited in China. In this study, 1163 adults in South China were recruited and urinary TCS concentrations were determined. TCS was detected in 99.5% of urine samples, indicating broad exposure in the study population. Urinary concentrations of TCS ranged from below the limit of detection (LOD) to 270 μg/L, with a median value of 3.67 μg/L. Urinary TCS concentrations from individuals were all lower than the Biomonitoring Equivalents reference dose, suggesting relatively low health risk in the participants. TCS concentrations did not differ significantly between sexes or education levels (p > 0.05). Nevertheless, marital status and age were found to be positively influence TCS levels (p < 0.001). After adjustment for body mass index (BMI), age was determined to be positively associated with TCS concentrations (p < 0.05), particularly in the age group from 31 to 51 years old. This study provides a baseline of urinary TCS exposure in South China general adult populations.
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Triclosan (TCS) is an antibacterial and antifungal agent used in many consumer products and exhibits a chemical structure similar to non-steroidal estrogen, which is known to induce endocrine disruption. Triclosan has been found in human plasma, urine, and breast milk, and the safety of TCS-containing products has been disputed. Although studies attempted to determine the estrogenic activity of TCS, no clear results have emerged. The aim of the present study was to examine estrogenic activity of TCS using an in vitro E-screen assay and an in vivo uterotrophic assay. The in vitro E-screen assay demonstrated that TCS significantly enhanced proliferation of MCF-7 breast cancer cells, although not in a concentration-dependent manner. The in vivo uterotrophic results showed no significant change in the weight of uteri obtained from TCS-administered Sprague-Dawley rats. Further, to understand the estrogenic activity attributed to TCS at the molecular level, gene-expression profiling of uterus samples was performed from both TCS- or estrogen-treated rats and the genes and cellular processes affected by TCS or estrogen were compared. Data demonstrated that both the genes and cellular processes affected by TCS or estrogen were significantly similar, indicating the possibility that TCS-mediated estrogenic activity occurred at the global transcriptome level. In conclusion, in vitro and gene-profiling results suggested that TCS exhibited estrogenic activity.
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The present study focuses on the successful preparation of microbial palladium nanoparticles (Pd-NPs). The even distribution of Pd in the periplasmic space of B. megaterium Y-4 cells is characterized using a transmission electronic microscopy (TEM) and scanning electron microscope (SEM). X-Ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) revealed the domination of Pd (0) in Pd-NPs. The microbial Pd-NPs were selected to detoxify triclosan (TCS). Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the intermediate products of dechlorination and oxidization. Free radicals quenching and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) capturing experiments confirmed the crucial contribution of atomic H• and O2·– to TCS degradation. Besides, TCS degradation by microbial Pd-NPs could alleviate the cytotoxicity of TCS polluted water. Meanwhile, great circulating utilization of microbial Pd-NPs was obtained in degrading TCS. Corresponding findings in the present study could provide new insight into the role of microbial Pd-NPs in detoxifying pollutants.
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Personal care products (PCPs) are generally used for personal hygiene, cleaning, grooming, and beautification. These include hair and skin care products, baby care products, UV blocking creams, facial cleansers, insect repellents, perfumes, fragrances, soap, detergents, shampoos, conditioners, toothpaste, etc., thus exposing humans easily. Personal preferences related to PCPs usage frequency are highly variable and depend on socioeconomic status and lifestyle factors. The increasing availability and diversity of PCPs from the retailer outlets consequently result in higher loading of PCPs into wastewater systems and, therefore, the environment. These compounds persistently and continuously release biologically active and inactive ingredients in the atmosphere, biosphere, geosphere, and demonstrating adverse effects on human, wild, and marine life. Advanced techniques such as granular activated carbon filtration and algae-based system may help biotransformation and remove PCP contaminants from water with improved efficiency. Additionally, harmony among PCPs related regulations of different countries may encourage standard checks to control their manufacturing, sale, and distribution across the borders to ensure consumers’ safety. Furthermore, all intended ingredients, their concentrations, and instructions for frequency of use as per age groups may be clearly labeled on packages of PCPs. In conclusion, the emerging environmental contaminants of PCPs and their association with the growing risks of negative effects on human health and globally on the environment emphasize the chemical-free simple lifestyle. © 2021, Iranian Journal of Pharmaceutical Research. All rights reserved.
Chapter
Many hundreds of endocrine disrupting chemicals (EDCs) have been measured as entering human breast tissue from a range of environmental sources, and this review focuses on discussion of mechanisms by which such EDCs may be contributing to the globally rising incidence of breast cancer. Many of the distinguishing features of breast cancer may be accounted for by EDC exposure, including, but not limited to, the fact that many EDCs possess estrogenic activity and exposure to estrogen is a main risk factor for breast cancer. Studies of the actions of EDCs in human breast cancer cells are aided by use of the conceptual framework of the hallmarks of cancer, and, acting by a variety of genomic and nongenomic mechanisms, EDCs have now been shown to enable all the hallmarks of cancer to develop in human breast cancer cells. Many studies report that hallmarks can develop at concentrations which are within the range of those measured in human breast tissues, especially when added as mixtures. The varied levels of different EDCs measured in individual breast tissue samples together with the overlapping and complementary mechanisms of action of the EDCs imply that thematic mechanisms will be driven inevitably by different chemical mixtures. Despite the complexity, EDCs do need to now be acknowledged as a risk factor for breast cancer in order for preventative strategies to include reduction in EDC exposure.
Chapter
This chapter discusses the potential for endocrine-disrupting chemicals (EDCs) to influence the development of cancer in female endocrine-sensitive tissues of the breast, endometrium, ovary, and cervix, and in male hormone-regulated tissues of the prostate, testis, and breast. Hanahan and Weinberg have established a framework for understanding the complexity of cancer development through their definition of hallmarks and enabling characteristics, and this offers the opportunity to explore the ability of complex environmental mixtures of EDCs to affect cancer. It is not necessary for each EDC to affect all the hallmarks, but if a mixture of EDCs can together affect all the hallmarks, and do so at environmentally relevant concentrations measurable in human tissues, then there is the potential for cancer development.
Chapter
This chapter provides an overview of the chemical components of personal care products (PCPs) that possess endocrine-disrupting activity and cites evidence that such endocrine-disrupting chemicals (EDCs) can be absorbed from application to human skin. Reported cases are described where absorption of EDCs from PCPs has affected human endocrine health. The use of PCPs presents high dermal exposure to multiple EDCs on a daily basis, and many of these EDCs have been measured in human tissue. Although it is not possible to identify the source of each EDC measured in human tissue, many of these chemicals are used only in PCPs, and several studies have found an association between concentrations measured in the tissue and self-reported use of PCPs. Dermal application of PCPs as a source of EDCs is an emerging issue, and national and international regulatory bodies are moving toward greater regulation of the component chemicals.
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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.
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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.
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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.
Preprint
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.
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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.
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A year into the coronavirus disease 2019 pandemic, the role of washing hands with soap and hand disinfectants is unavoidable as a primary way to control the infection spread in communities and healthcare facilities. The extraordinary surge in demand for handwashing products has led to environmental concerns. Since soaps are complex mixtures of toxic and persistent active ingredients, the prudent option is to promote eco-friendly replacements for the current products. On the other hand, with the increase in soap packaging waste production, soap packaging waste management and recycling become essential to reduce environmental impact. This systematic review aimed to collect some recent methods for identifying biodegradable and sustainable raw materials to produce and package cleaning agents, especially soap.
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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.
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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.
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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.
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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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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).
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
A sensitive method for the determination of triclosan in plasma and milk is presented. Following hydrolysis of possible conjugates, triclosan is extracted with n-hexane/acetone, partitioned into alcoholic potassium hydroxide, and converted into its pentafluorobenzoyl ester. After sulfuric acid cleanup, sample extracts are analyzed by gas chromatography/electron capture negative ionization mass spectrometry. The limit of quantification was 0.009 ng/g for a 5-g plasma sample and 0.018 ng/g for a 3-g milk sample. The coefficient of variation for the method was 6%. The method was tested on more than 70 human plasma and milk samples, of which all plasma samples and more than half of the milk samples were above the limit of quantification. The presented method has lowered the limit of quantification for triclosan in human matrixes significantly as compared to previous methods and makes possible the analysis of triclosan in humans under normal exposure conditions.
Risker och nytta med triklosan i tandkräm [Risks and benefits with triclosan containing toothpastes]
  • S Edwardsson
  • L M Burman
  • Backman
Edwardsson S, Burman L, Adolfsson-Erici M, Backman N. Risker och nytta med triklosan i tandkräm [Risks and benefits with triclosan containing toothpastes]. Tandlakartidningen 2005;97:58–64.
Determination of triclosan as its pentafluorobenzoyl ester in human plasma and milk using electron capture negative ionization mass spectrometry Clinical evidence for the lack of triclosan accumulation from daily use in dentifrices
  • M Allmyr
  • Mclachlan Ms
  • G Sandborgh-Englund
  • Dm Bagley
  • Lin
  • Yj
Allmyr M, McLachlan MS, Sandborgh-Englund G, Adolfsson-Erici M. Determination of triclosan as its pentafluorobenzoyl ester in human plasma and milk using electron capture negative ionization mass spectrometry. Anal Chem 2006, ___________________ doi:10.1021/ac060666x. Bagley DM, Lin YJ. Clinical evidence for the lack of triclosan accumulation from daily use in dentifrices. Am J Dent 2000;13: 148–52.
Screening av triclosan och vissa bromerade fenoliska ämnen i Sverige. [Screening of triclosan and some brominated, phenolic compounds in Sweden
  • Remberger M J Sternbeck
  • Strömberg
Remberger M, Sternbeck J, Strömberg K. Screening av triclosan och vissa bromerade fenoliska ämnen i Sverige. [Screening of triclosan and some brominated, phenolic compounds in Sweden]. IVL Rapp 2002:B1477-2.
Risker och nytta med triklosan i tandkräm [Risks and benefits with triclosan containing toothpastes]
  • Edwardsson
Screening av triclosan och vissa bromerade fenoliska ämnen i Sverige. [Screening of triclosan and some brominated, phenolic compounds in Sweden]
  • Remberger