Triclosan: A critical review of the experimental data and development of margins of safety for consumer products

Abstract

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.

Keywords::

• Exposure assessment
• margin of safety
• PPAR
• safety assessment
• triclosan

Acknowledgments

The authors wish to thank Christopher Saranko, PhD, and Annette Santamaria, PhD, for assistance with the consumer product–based exposure estimates; Robinan Gentry, PhD, for assistance with the kinetic studies and Dr. Gentry and Cynthia Van Landingham, MS, for assistance with the biomonitoring-based exposure estimates and dose-response modeling; and Sara Oglesbee for editorial assistance.

Declaration of interests

Joseph Rodricks, PhD, and Annette Shipp, PhD, are Principals with ENVIRON International Corporation; both provide toxicological consulting services to private and public sector clients. James A. Swenberg, DVM, PhD, is a Kenan Distinguished Professor at the University of North Carolina at Chapel Hill. Joseph Borzelleca, PhD, is an Emeritus Professor at Virginia Commonwealth University School of Medicine. Robert Maronpot, DVM, MS, MPH, is retired from the National Institutes of Environmental Health Sciences. Each of these individuals provides consulting services in the disciplines of toxicology and/or pathology to private and public sector clients. The manuscript was prepared with financial support from the Colgate Palmolive Company, a corporation that manufactures and sells a wide variety of consumer products, some of which contain triclosan. The authors have the sole responsibility for the contents of this paper. The views and opinions expressed in this paper may not necessarily be those of the Colgate Palmolive Company.