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Triclosan: A Critical Review Of The Experimental Data And Development Of Margins Of Safety For Consumer Products

//Triclosan: A Critical Review Of The Experimental Data And Development Of Margins Of Safety For Consumer Products

Triclosan: A Critical Review Of The Experimental Data And Development Of Margins Of Safety For Consumer Products

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Joseph V. Rodricks, James A. Swenberg, Joseph F. Borzelleca, Robert R. Maronpot, and Annette M. Shipp
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Triclosan (2,4,4′-trichloro-2′-hydroxy-diphenyl ether) is an antibacterial compound that has been used in consumer products for about 40 years. The tolerability and safety of triclosan has been evaluated in human volunteers with little indication of toxicity or sensitization. Although information in humans from chronic usage of personal care products is not available, triclosan has been extensively studied in laboratory animals. When evaluated in chronic oncogenicity studies in mice, rats, and hamsters, treatment-related tumors were found only in the liver of male and female mice. Application of the Human Relevance Framework suggested that these tumors arose by way of peroxisome proliferator-activated receptor α (PPARα) activation, a mode of action not considered to be relevant to humans. Consequently, a Benchmark Dose (BMDL10) of 47 mg/kg/ day was developed based on kidney toxicity in the hamster. Estimates of the amount of intake from in the use of representative personal care products for men, women, and children were derived in two ways: (1) using known or assumed triclosan levels in various consumer products and assumed usage patterns (product-based estimates); and (2) using upper bound measured urinary triclosan levels from human volunteers (biomonitoring-based estimates) using data from the Centers for Disease Control and Prevention. For the product-based estimates, the margin of safety (MOS) for the combined exposure estimates of intake from the use of all triclosan-containing products considered were approximately 1000, 730, and 630 for men, women, and children, respectively. The MOS calculated from the biomonitoring-based estimated intakes were 5200, 6700, and 11,750 for men, women, and children, respectively. Based on these results, exposure to triclosan in consumer products is not expected to cause adverse health effects in children or adults who use these products as intended.

Introduction

Triclosan (2,4,4′-trichloro-2′-hydroxy-diphenyl ether) is an antibacterial ingredient also known as Irgasan DP300, FAT 80′023, CH 3565, GP41-353, and Irgacare MP (the pharmaceutical grade of triclosan that is > 99% pure). Triclosan has been used in consumer products since 1968 and in dental products since the 1980s in Europe (EU) and the mid-1990s in the United States (US) following approval by the US Food and Drug Administration (FDA) (FDA, 2006). In 1989, it was approved for use in cosmetics at levels up to 0.3% by the European Community Cosmetic Directive (EU, 2007).

Triclosan is used in numerous personal care products, including toothpastes, antibacterial soaps (bars and liquids), deodorant soaps (bars and liquids), cosmetic and antiseptic products, and antiperspirants/deodorants (EU, 2007). Triclosan is also found in cleaning supplies and is infused in an increasing number of consumer products, such as kitchen utensils, toys, bedding, clothes, fabrics, and trash bags. Showering or bathing with 2% triclosan has become a recommended regime for the decolonization of patients whose skin is carrying methicillin-resistant Staphylococcus aureus (MRSA) (Coia et al., 2006) following the successful control of MRSA outbreaks in several clinical settings (Brady et al., 1990; Zafar et al., 1995).

Biomonitoring studies have identified triclosan in urine, plasma, and breast milk of humans (Adolfsson-Erici et al., 2002; Allmyr et al., 2006; Dayan, 2007; Wolff et al., 2007; Calafat et al., 2008) but typically without attribution to specific sources of triclosan exposure. Calafat and coworkers (2008) reported the amount of triclosan in the urine of human volunteers who participated in the National Health and Nutrition Examination Survey (NHANES) 2003–2004 (CDC, 2005). NHANES is an ongoing survey conducted annually since 1999 by the US Centers for Disease Control and Prevention (CDC) designed to gather data on selected chemicals, including triclosan, to be used to assess the health and nutritional status of the general US population. As part of this survey, urinary data were collected for adult men and women and children between the ages of 6 and 11.

The safety of triclosan has been evaluated in clinical trials and in other studies with human volunteers designed to assess tolerability and/or kinetics. Although results from these studies indicated that triclosan can be used safely with good tolerability at levels found in current personal care products, no long-term follow-up of potential chronic effects in workers, both those producing triclosan and those manufacturing consumer products containing triclosan, or the general population who use triclosan-containing products has been conducted. Triclosan has been extensively studied, however, in experimental animals, primarily by the oral and dermal routes of exposure with acute, subacute, subchronic, and chronic administration.

This investigation was conducted to (1) critically evaluate available information and data that can be used to assess the safety of triclosan and to develop intake values, such as experimentally derived no observed adverse effect levels (NOAELs) or Benchmark doses (BMDs) derived using appropriate dose-response models; (2) estimate the amount of daily intake of triclosan from consumer products using typical exposure algorithms and exposure factors and the amount of daily intake of triclosan estimated using the NHANES 2003–2004 (CDC, 2005) biomonitoring data; (3) compare estimates of daily triclosan intake to appropriate intake values (e.g., a NOAEL or BMD) to derive a ratio, termed a margin of safety (MOS); and (4) provide a context for the calculated exposures through a safety characterization in which the magnitude of these MOS are discussed.

This study was based on the methods described in regulatory guidance for the conduct of safety or risk assessments (USEPA, 1987, 1997, 2000, 2005).

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2017-01-11T22:13:35+00:00