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Urinary Concentrations of the Antibacterial Agent Triclocarban in United States Residents: 2013–2014 National Health and Nutrition Examination Survey Xiaoyun Ye, Lee-Yang Wong, Prabha Dwivedi, Xiaoliu Zhou, Tao Jia, and Antonia M. Calafat Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.6b04668 • Publication Date (Web): 22 Nov 2016 Downloaded from http://pubs.acs.org on November 22, 2016
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Environmental Science & Technology
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Urinary Concentrations of the Antibacterial Agent Triclocarban in United States
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Residents: 2013–2014 National Health and Nutrition Examination Survey
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Xiaoyun Ye, Lee-Yang Wong, Prabha Dwivedi, Xiaoliu Zhou, Tao Jia, and Antonia M.
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Calafat
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Division of Laboratory Sciences, National Center for Environmental Health, Centers for
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Disease Control and Prevention, Atlanta, GA 30341
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*Corresponding Author
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Xiaoyun Ye
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Centers for Disease Control and Prevention
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4770 Buford Hwy, Mailstop F53
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Atlanta, GA 30341
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770-488-7502
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[email protected] 17 18
Key Words: antibacterial agents, biomonitoring, exposure, human, NHANES 2013–
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2014, triclocarban.
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Disclaimer: The findings and conclusions in this report are those of the authors and do
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not necessarily represent the official position of the Centers for Disease Control and
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Prevention (CDC). Use of trade names is for identification only and does not imply
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endorsement by the CDC, the Public Health Service, or the US Department of Health and
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Human Services.
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Manuscript Graphics
Exposure to Triclocarban in General U.S. Population 95th percentile concentrations by demographic characteristics in NHANES 2013-2014
95th percentile triclocarban conc.
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non-adjusted (μg/L) creatinine adjusted (μg/g)
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(Error bars indicate 95% confidence intervals)
50 40 30 20 10 0
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Abstract
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Triclocarban is widely used as an antibacterial agent in personal care products, and the
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potential for human exposure exists. We present here the first nationally representative
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assessment of exposure to triclocarban among Americans ≥ 6 years of age who
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participated in the 2013–2014 National Health and Nutrition Examination Survey. We
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detected triclocarban at concentrations above 0.1 µg/L in 36.9% of 2,686 urine samples
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examined. Triclocarban was detected more frequently in adolescents and adults than in
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children, and in non-Hispanic black compared to other ethnic groups. In univariate
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analysis, log-creatinine, sex, age, race, and body surface area (BSA) were significantly
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associated with the likelihood of having triclocarban concentrations above the 95th
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percentile. In multiple regression models, persons with BSA at or above the median
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(≥1.86 m2) were 2.43 times more likely than others, and non-Hispanic black and non-
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Hispanic white were 3.71 times and 2.23 times more likely than “all Hispanic,”
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respectively, to have urinary concentrations above the 95th percentile. We found no
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correlations between urinary concentrations of triclocarban and triclosan, another
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commonly used antibacterial agent. Observed differences among demographic groups
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examined may reflect differences in physiological factors (i.e., BSA) as well as use of
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personal care products containing triclocarban.
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Introduction 3, 4, 4’-Trichlorocarbanilide (triclocarban) is used as an antibacterial agent in a
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variety of consumer and personal care products including bar soap, detergent, deodorant,
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shaving cream, and shampoo (1-3). Several studies listed triclocarban as active
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ingredient in about 85% of antibacterial bar soaps examined in the US market, with levels
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ranging between 0.5 percent (or 0.005 g/g) and 1.5 percent (or 0.015 g/g) (4, 5). Triclocarban
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is also used in cleansing preparations in hospitals and other medical settings where the
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potential risk for the transmission of infections is high (3).
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Human exposure to triclocarban occurs mainly through dermal contact; inhalation
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of triclocarban-containing dust and ingestion of triclocarban contaminated water and food
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may also occur (6, 7). The potential adverse health effects of triclocarban in humans are
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still largely unknown, but previous studies suggested that triclocarban could act as an
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endocrine disruptor, both in cell-based assays and in rats (8-14) and induced breast cell
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pre-malignancy as a co-carcinogen (15). The reference dose in humans, calculated using
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the no adverse effect level from a 2 year chronic toxicity rat study, is 0.025 mg kg bw-1 d
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(16). Epidemiologic data are limited to one study—to evaluate prenatal exposure to
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triclocarban, triclosan and parabens and potential adverse birth outcomes in an immigrant
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population of mothers and their neonates—which reported suggestive associations (albeit
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no longer present in sensitivity analyses) for triclocarban (17). Furthermore, recent
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studies suggested that triclocarban could potentially contribute to bacterial resistance to
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antibiotics (18).
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Early research on the metabolism of triclocarban in rats indicated that the major biliary and fecal metabolites were free and conjugated triclocarban and 2’-hydroxy-
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triclocarban (19, 20). In a previous study, we also identified free and conjugated
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triclocarban, 3’-hydroxy-triclocarban, and 2’-hydroxy-triclocarban as the major urine and
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serum metabolites in Sprague Dawley rats (21). Data on the metabolism of triclocarban
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in humans also exist (22-24). In a group of six healthy volunteers, after taking a shower
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with commercial 0.6% triclocarban containing soap, N-glucuronide triclocarban was the
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major urinary metabolite (24). Therefore, concentrations of urinary species of
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triclocarban have been used as valid biomarkers of exposure (21, 25-32).
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Because of the well-known use of triclocarban in personal care and consumer
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products and the environmental persistence of this chemical, triclocarban has been
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detected in the environment (6, 7, 33-36) and the potential for human exposure to this
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chemical exists. Of interest, however, exposure to triclocarban in the United States may
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change in the future. In September 2016, the U.S. Food and Drug Administration (FDA)
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issued a final rule establishing that triclocarban and 18 other active ingredients used in
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over-the-counter antiseptic wash products (e.g., hand washes, body washes) can no
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longer be marketed (37). To increase the understanding of the extent of exposure to
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triclocarban and to set reference ranges which may be used to evaluate whether FDA’s
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rule impacts exposure to triclocarban in the future, we measured the urinary
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concentrations of triclocarban in participants of the 2013–2014 National Health and
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Nutrition Examination Survey (NHANES). We also examined the associations between
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sociodemographic and physiological factors and triclocarban concentrations.
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Materials and Methods NHANES, conducted annually since 1999 by the National Center for Health
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Statistics (NCHS) at the Centers for Disease Control and Prevention (CDC), is an
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ongoing survey designed to measure the health and nutritional status of the civilian
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noninstitutionalized U.S. population (38). The survey includes household interviews,
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standardized physical examinations, and collection of medical histories and biologic
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specimens, some of which are used to assess exposure to environmental chemicals (38).
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The NCHS Research Ethics Review Board reviewed and approved the NHANES study
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protocol. All participants gave informed written consent; parents or guardians provided
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consent for participants 37%) than in children (22.0%), and more frequently in non-
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Hispanic black (64.1%) than in the other ethnic groups (28.7%–33.6%). Non-Hispanic
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black is the only demographic group with geometric mean above the LOD, at 0.397 µg/L
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(0.293 µg/g creatinine) (Table 1). We also detected triclocarban more frequently among
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low household income persons (
