Urinary Concentrations of Triclosan in the U.S.
Urinary Concentrations of Triclosan in the U.S.
Background: Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware.
Objectives: This study was designed to assess exposure to triclosan in a representative sample ≥ 6 years of age of the U.S. general population from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) .
Methods: We analyzed 2,517 urine samples using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry.
Results: We detected concentrations of total (free plus conjugated) triclosan in 74.6% of samples at concentrations of 2.4-3,790 µg/L. The geometric mean and 95th percentile concentrations were 13.0 µg/L (12.7 µg/g creatinine) and 459.0 µg/L (363.8 µg/g creatinine) , respectively. We observed a curvilinear relation between age and adjusted least square geometric mean (LSGM) concentrations of triclosan. LSGM concentrations of triclosan were higher in people in the high household income than in people in low (p < 0.01) and medium (p = 0.04) income categories.
Conclusions: In about three-quarters of urine samples analyzed as part of NHANES 2003-2004, we detected concentrations of triclosan. Concentrations differed by age and socioeconomic status but not by race/ethnicity and sex. Specifically, the concentrations of triclosan appeared to be highest during the third decade of life and among people with the highest household incomes.
Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a synthetic, broad-spectrum antimicrobial agent that has been used extensively for more than 20 years in a variety of consumer products, including toothpaste, mouthwash, deodorants, soaps, textiles (e.g., socks, underwear), toys, liquid dishwashing soap, and plastic kitchenware (Adolfsson-Erici et al. 2002; Bhargava and Leonard 1996; Jones et al. 2000; National Library of Medicine 2007; Perencevich et al. 2001). In Europe, about 350 tons of triclosan are produced annually for commercial applications (Singer et al. 2002). In the United States, 76% of 395 commercial soaps examined contained triclosan (Perencevich et al. 2001). Despite its widespread use, the efficacy of triclosan-containing products in household and other non-health care-related settings and the potential hazards associated with this use, such as the emergence of antibiotic-resistant bacteria, are the subject of an ongoing scientific and public debate (Aiello et al. 2007; Jones et al. 2000; Kampf and Kramer 2004; Russell 2003; Weber and Rutala 2006; Yazdankhah et al. 2006).
Triclosan has been detected in the aquatic environment and in some food sources (Lindstrom et al. 2002; Lopez-Avila and Hites 1980; McAvoy et al. 2002; Okumura and Nishikawa 1996; Singer et al. 2002), and has attracted interest as an environmental contaminant (Halden and Paull 2005). In frogs, triclosan can disrupt thyroid hormone-associated gene expression and induce changes in the thyroid hormone-mediated metamorphosis process (Veldhoen et al. 2006). Triclosan can also alter circulating serum concentrations of total thyroxine in rats (Crofton et al. 2007). Triclosan is not acutely toxic to mammals (Bhargava and Leonard 1996), but it can interact with cytochrome P450-dependent enzymes, UDP-glucuronosyltransferases, and the human pregnane X receptor (Hanioka et al. 1996; Jacobs et al. 2005; Wang et al. 2004). The relevance of these interactions is unknown.
Information about the known commercial uses of triclosan indicates that ingestion and dermal absorption are the most likely routes of exposure (Moss et al. 2000; Sandborgh-Englund et al. 2006). Radioactive triclosan is excreted in feces, and to a lesser extent in urine, after topical exposure in rats (Moss et al. 2000) and oral administration in mice (Kanetoshi et al. 1988). The extent of dermal absorption of triclosan was examined both in vitro and in vivo in rats and humans (Moss et al. 2000). In vitro, 24 hr after application, about 6.3% of triclosan had penetrated human skin compared with 23% for rat skin. These data suggest that dermal absorption of triclosan in humans is lower than in rats. In all cases, glucuronidation and to a lesser extent sulfation of triclosan occurred during passage through the skin. No oxidative metabolites were detected in the urine in vivo or after absorption through skin in vitro; the major urinary metabolites were triclosan glucuronide and sulfate (Moss et al. 2000). In another study, 10 healthy adult Swedish volunteers (50% males; median age, 28 years) were exposed to a single oral dose of 4 mg triclosan by swallowing an oral mouthwash solution, and the volunteers' plasma and urinary concentrations of triclosan were determined (Sandborgh-Englund et al. 2006). Triclosan concentrations in plasma increased rapidly, with a maximum concentration within 1-3 hr; the estimated terminal plasma half-life was 21 hr. The major fraction of the triclosan dose was excreted in urine within the first 24 hr (calculated urinary excretion half-life was 11 hr), and approached baseline levels within 8 days after exposure. A median oral dose of 54% was excreted in urine within the first 4 days after exposure. The percentage of free triclosan in plasma was higher than in urine; in urine, triclosan was excreted mostly in its conjugated forms. These data suggest that the concentrations of triclosan in urine (conjugated and free species) can be used as biomarkers of exposure to triclosan.
The widespread use of triclosan has raised interest about assessing human exposure to this compound. Therefore, we measured the urinary concentration of triclosan in participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2004 to obtain the first nationally representative concentration of triclosan in the United States.
Abstract and Introduction
Abstract
Background: Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware.
Objectives: This study was designed to assess exposure to triclosan in a representative sample ≥ 6 years of age of the U.S. general population from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) .
Methods: We analyzed 2,517 urine samples using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry.
Results: We detected concentrations of total (free plus conjugated) triclosan in 74.6% of samples at concentrations of 2.4-3,790 µg/L. The geometric mean and 95th percentile concentrations were 13.0 µg/L (12.7 µg/g creatinine) and 459.0 µg/L (363.8 µg/g creatinine) , respectively. We observed a curvilinear relation between age and adjusted least square geometric mean (LSGM) concentrations of triclosan. LSGM concentrations of triclosan were higher in people in the high household income than in people in low (p < 0.01) and medium (p = 0.04) income categories.
Conclusions: In about three-quarters of urine samples analyzed as part of NHANES 2003-2004, we detected concentrations of triclosan. Concentrations differed by age and socioeconomic status but not by race/ethnicity and sex. Specifically, the concentrations of triclosan appeared to be highest during the third decade of life and among people with the highest household incomes.
Introduction
Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a synthetic, broad-spectrum antimicrobial agent that has been used extensively for more than 20 years in a variety of consumer products, including toothpaste, mouthwash, deodorants, soaps, textiles (e.g., socks, underwear), toys, liquid dishwashing soap, and plastic kitchenware (Adolfsson-Erici et al. 2002; Bhargava and Leonard 1996; Jones et al. 2000; National Library of Medicine 2007; Perencevich et al. 2001). In Europe, about 350 tons of triclosan are produced annually for commercial applications (Singer et al. 2002). In the United States, 76% of 395 commercial soaps examined contained triclosan (Perencevich et al. 2001). Despite its widespread use, the efficacy of triclosan-containing products in household and other non-health care-related settings and the potential hazards associated with this use, such as the emergence of antibiotic-resistant bacteria, are the subject of an ongoing scientific and public debate (Aiello et al. 2007; Jones et al. 2000; Kampf and Kramer 2004; Russell 2003; Weber and Rutala 2006; Yazdankhah et al. 2006).
Triclosan has been detected in the aquatic environment and in some food sources (Lindstrom et al. 2002; Lopez-Avila and Hites 1980; McAvoy et al. 2002; Okumura and Nishikawa 1996; Singer et al. 2002), and has attracted interest as an environmental contaminant (Halden and Paull 2005). In frogs, triclosan can disrupt thyroid hormone-associated gene expression and induce changes in the thyroid hormone-mediated metamorphosis process (Veldhoen et al. 2006). Triclosan can also alter circulating serum concentrations of total thyroxine in rats (Crofton et al. 2007). Triclosan is not acutely toxic to mammals (Bhargava and Leonard 1996), but it can interact with cytochrome P450-dependent enzymes, UDP-glucuronosyltransferases, and the human pregnane X receptor (Hanioka et al. 1996; Jacobs et al. 2005; Wang et al. 2004). The relevance of these interactions is unknown.
Information about the known commercial uses of triclosan indicates that ingestion and dermal absorption are the most likely routes of exposure (Moss et al. 2000; Sandborgh-Englund et al. 2006). Radioactive triclosan is excreted in feces, and to a lesser extent in urine, after topical exposure in rats (Moss et al. 2000) and oral administration in mice (Kanetoshi et al. 1988). The extent of dermal absorption of triclosan was examined both in vitro and in vivo in rats and humans (Moss et al. 2000). In vitro, 24 hr after application, about 6.3% of triclosan had penetrated human skin compared with 23% for rat skin. These data suggest that dermal absorption of triclosan in humans is lower than in rats. In all cases, glucuronidation and to a lesser extent sulfation of triclosan occurred during passage through the skin. No oxidative metabolites were detected in the urine in vivo or after absorption through skin in vitro; the major urinary metabolites were triclosan glucuronide and sulfate (Moss et al. 2000). In another study, 10 healthy adult Swedish volunteers (50% males; median age, 28 years) were exposed to a single oral dose of 4 mg triclosan by swallowing an oral mouthwash solution, and the volunteers' plasma and urinary concentrations of triclosan were determined (Sandborgh-Englund et al. 2006). Triclosan concentrations in plasma increased rapidly, with a maximum concentration within 1-3 hr; the estimated terminal plasma half-life was 21 hr. The major fraction of the triclosan dose was excreted in urine within the first 24 hr (calculated urinary excretion half-life was 11 hr), and approached baseline levels within 8 days after exposure. A median oral dose of 54% was excreted in urine within the first 4 days after exposure. The percentage of free triclosan in plasma was higher than in urine; in urine, triclosan was excreted mostly in its conjugated forms. These data suggest that the concentrations of triclosan in urine (conjugated and free species) can be used as biomarkers of exposure to triclosan.
The widespread use of triclosan has raised interest about assessing human exposure to this compound. Therefore, we measured the urinary concentration of triclosan in participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2004 to obtain the first nationally representative concentration of triclosan in the United States.
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