Triclosan and triclocarban in consumer products
Triclosan and triclocarban are antibacterial chemicals used in many consumer products, from dish soap to toothpaste, although the benefits of adding these compounds to consumer products is unclear. Triclosan kills bacteria by inhibiting fatty acid biosynthesis and remodeling, and it may contribute to antimicrobial resistance. Much less is known about triclocarban, but it is generally assumed to disrupt bacterial cell membrane integrity.
Both triclosan and triclocarban are found in streams across the country. Also, they are present in sewage sludge that is applied to farmland and according to a recent Centers for Disease Control and Prevention (CDC) study, triclosan was detected in the urine of nearly 75% of 2,517 people tested, indicating broad exposure. Due to their toxicological profiles, and persistence in the environment, these chemicals pose a potential risk to human health and the environment.
Because triclosan and triclocarban are used in so many consumer products, human and environmental exposures are ubiquitous. Consumer products that contain triclosan or triclocarban are generally labeled “antibacterial”, “fights odors”, “improves skin”, or “kills germs”. Most uses of triclosan are regulated by the U.S. Food and Drug Administration (FDA), including the use of triclosan in such products as bar, liquid and foaming soaps, underarm deodorants, toothpastes, mouthwashes, shampoos, cosmetics, laundry detergents, fabric softeners, facial tissues, antiseptics for wound care, and animal grooming products. Triclosan is also registered by the U.S. Environmental Protection Agency (EPA) for use as a pesticide, but most of these uses involve the incorporation of triclosan in consumer products as a bacteriostat, fungistat, mildewistat, and deodorizer. Examples of products regulated by EPA that may contain triclosan include such plastic products as toys, toothbrushes, shower curtains and cutting boards—as well as carpets, mattresses, clothing, brooms, mulch, floors, awnings, tents, toilet bowls, urinals, garbage cans, refuse container liners, insulation, concrete mixtures, grouts, and upholstery fabrics.
In contrast, triclocarban is not registered as a pesticide, rather it can be found in products regulated by the FDA, including bar, liquid and foaming soaps, underarm deodorants, shampoos and shaving creams.
Environmental Fate and Health Hazards
Occurrence in the Environment
In a national stream survey conducted in 1999 and 2000, the U.S. Geological Survey (USGS) detected triclosan in 58% of streams tested. In a recent, smaller study, samples taken from streams in the Greater Baltimore region, detected triclosan and triclocarban in similar concentrations, suggesting that because of shared usage, disposal and environmental fate, co-occurrence of triclosan and triclocarban can be expected. Both triclosan and triclocarban can bioaccumulate and can be toxic to microalgae, important constituents of aquatic ecosystem food webs.
Both of these compounds are found in sewage sludge, which is generally applied to land. While there is evidence that triclosan can leach from the biosolids into surrounding soil and groundwater and be taken up by biota, similar studies on the fate and transport of triclocarban are lacking. Two concerns that have been raised regarding the widespread environmental distribution of triclosan and triclocarban are promotion of bacterial resistance, and hormone disruption in vertebrates.
Triclosan functions by inactivating an enzyme, enoyl reductase, that is needed for fatty acid biosynthesis for the maintenance of cell membrane integrity. Antibacterial resistance to triclosan can be demonstrated under laboratory conditions. However, evidence for the development of resistance to triclosan under common environmental conditions is lacking. Concerns for the development of resistance are based on the widespread and persistent presence of sublethal concentrations in the environment.
Hormone disruption in fish has been documented in rivers and water bodies throughout the U.S., primarily in waters impacted by sewage treatment plant discharges, although cause and effect linkage with these chemicals in the field remain unclear. In laboratory studies, triclosan acts like weak estrogen in organisms while triclocarban has been shown to augment the activity of testosterone. Fish exposure studies first identified concerns regarding triclosan's endocrine disrupting potential. After exposures ranging from 1 – 100 parts per billion, the medaka fry (Oryzias latipes), a species of fish commonly used for toxicity testing, exhibited changes in fin length and sex ratio. Triclosan was found to be highly toxic in early life stages of the medaka, reducing hatching success and delaying hatching time. Also, in this study, triclosan induced vitellogenin production in male fish (vitellogenin is a component of the yolk sac in eggs normally only produced by the females). Similar concerns were found in South African clawed frogs (Xenopus laevis), a common test species, as male frogs injected with triclosan-synthesized vitellogenin and had reduced testosterone levels. A separate study using bullfrogs demonstrated triclosan's ability to bind to the thyroid hormone receptor and in rodents, triclosan administered for 31 days beginning shortly after weaning reduces thyroxin levels in male pubertal rats
Both triclosan and triclocarban can bioaccumulate and are extremely toxic to microalgae, important constituents of aquatic ecosystem food webs. The release of triclosan and triclocarban into the environment is of concern, not only for its potential impact on the environment, but for its significant potential to act in combination with other hormone disrupting chemicals.
Human Health Exposure and Hazard
Human exposure to triclosan and triclocarban results from skin exposure or incidental ingestion (that is, swallowing toothpaste or mouth wash that contain triclosan, or possibly contaminated tap water). In addition to detection in human urine, several reports from the U.S. and Europe demonstrate that triclosan is present in human milk.
Currently, there are no studies on the effects of exposure in infants. There is limited evidence that triclosan may be a weak developmental toxicant, based on a single unpublished rodent study. There is some evidence that triclosan, which is structurally similar to thyroid hormones, can disrupt thyroid hormone production in rats and triclosan binds to both the estrogen and androgen receptors, resulting in displacement of respective hormones. Triclocarban was found to enhance the activities of testosterone in rats when administered in combination with testosterone; in a 10-day exposure study, this combination significantly increased the size of all male sex accessory organs, compared to testosterone or triclocarban treatments alone.
Based on the limited availability of data, it is not possible to classify the genotoxicity, mutagenicity, and carcinogenicity status of triclosan. In a recent in vitro study, triclosan was shown to alter human breast cell growth. Additional studies are needed to characterize the potential effects of triclosan on breast tissue and breast cancer, particularly given that there is widespread human exposure to triclosan.
Risks versus Benefits of Triclosan and Triclocarban
Studies have demonstrated that products with triclosan were no more effective at killing bacteria than soap and water. Also, there is evidence that the use of triclosan can accelerate the development of bacteria that are resistant to antibiotics, a major public health concern. Because the statements used on the label of most triclosan-containing products are very general (e.g., “non-public health” uses, “antibacterial” and “fights odors”), efficacy data is not required for registration of triclosan by the U.S. Environmental Protection Agency. Triclocarban is no longer used registered as a pesticide, despite its continued use in many consumer products. Its current use in personal care products and cosmetics is, however, regulated by the U.S. Food and Drug Administration.
- ^Kolpin, D. W., Furlong, E. T., Meyer, M. T., Thurman, E. M., Zaugg, S. F., Barber, L. B., and Buxton, H. T. 2002. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. Environ. Sci. Technol. 36(6):1202-1211.
- ^Halden, R. U., and Paull, D. H. 2005. Co-occurrence of triclocarban and triclosan in U.S. water resources. Environ Sci Technol. 39(6):1420-6.
- ^Yang, L. H., Ying, G. G., Su, H. C., Stauber, J. L., Adams, M. S., and Binet, M. T. 2008. Growth-inhibiting effects of 12 antibacterial agents and their mixtures on the freshwater microalga Pseudokirchneriella subcapitata. Environ Toxicol Chem. 27(5):1201-8.
- ^Chu, S., and Metcalfe, C. D. 2007. Simultaneous determination of triclocarban and triclosan in municipal biosolids by liquid chromatography tandem mass spectrometry. J Chromatogr A. 1164(1-2):212-8.
- ^Lapen, D. R., Topp, E., Metcalfe, C. D., Li, H., Edwards, M., Gottschall, N., Bolton, P., Curnoe, W., Payne, M., and Beck, A. Pharmaceutical and personal care products in tile drainage following land application of municipal biosolids. Sci Total Environ. 399(1-3):50-65.
- ^Kinney, C. A., Furlong, E. T., Kolpin, D. W., Burkhardt, M. R., Zaugg, S. D., Werner, S. L., Bossio, J. P., and Benotti, M.J. 2008. Bioaccumulation of pharmaceuticals and other anthropogenic waste indicators in earthworms from agricultural soil amended with biosolid or swine manure. Environ. Sci. Technol. 42(6):1863-70.
- ^Xu, H., Sullivan, T.J., Sekiguchi, J., Kirikae, T., Ojima, I., Stratton, C.F., Mao, W., Rock, F.L., Alley, M.R., Johnson, F., Walker ,S.G., Tonge, P.J. 2008. Mechanism and inhibition of saFabI, the enoyl reductase from Staphylococcus aureus. Biochemistry. 47(14):4228-36.
- ^Foran, C. M., Bennett, E. R., and Benson, W. H. 2000. Developmental evaluation of a potential non-steroidal estrogen: triclosan. Marine Environ Res. 50:153-156.
- ^ Ishibashi, H,, Matsumura, N., Hirano, M., Matsuoka, M., Shiratsuchi, H., Ishibashi, Y., Takao, Y., and Arizono, K. 2004. Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin. Aquat. Toxicol. 67(2):167-79.
- ^Matsumura, N., Ishibashi, H., Hirano, M., Nagao, Y., Watanabe, N., Shiratsuchi, H., Kai, T., Nishimura, T., Kashiwagi, A., and Arizono, K. 2005. Effects of nonylphenol and triclosan on production of plasma vitellogenin and testosterone in male South African clawed frogs (Xenopus laevis). Biol. Pharm. Bull. 28(9):1748-51.
- ^Veldhoen, N., Skirrow, R. C., Osachoff, H., Wigmore, H., Clapson, D. J., Gunderson, M. P., Van Aggelen, G., and Helbing, C. C. 2006. The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development. Aquat. Toxicol. 80(3):217-27; Zorrilla, L.M., Gibson, E.K., Jeffay, S.C., Crofton, K.M., Setzer, W.R., Cooper , R.L., Stoker, T.E. 2008. The effects of triclosan on puberty and thyroid hormones in male Wistar rats. Toxicol. Sci. Advance Access published online on October 21, 2008, doi:10.1093/toxsci/kfn225.
- ^Coogan, M.A., and La Point, T. W. 2008. Snail bioaccumulation of triclocarban, triclosan, and methyl-triclosan in a North Texas, USA, stream affected by wastewater treatment plant runoff. Environ Toxicol Chem. 27(8):1788-1793.
- ^ Yang, L. H., Ying, G. G., Su, H. C., Stauber, J. L., Adams, M. S., and Binet, M. T. 2008. Growth-inhibiting effects of 12 antibacterial agents and their mixtures on the freshwater microalga Pseudokirchneriella subcapitata. Environ Toxicol Chem. 27(5):1201-8.
- ^Loraine, G. A., and Pettigrove, M. E. 2006. Seasonal variations in concentrations of pharmaceuticals and personal care products in drinking water and reclaimed wastewater in southern California. Environ Sci Technol. 40(3):687-95.
- ^Gee, R. H., Charles, A., Taylor, N., and Darbre, P. D. 2008. Oestrogenic and androgenic activity of triclosan in breast cancer cells. J. Appl. Toxicol. 28:78-91.
- ^Ahn, K. C., Zhao, B., Chen, J., Cherednichenko, G., Sanmarti, E., Denison, M. S., Lasley, B., Pessah, I. N., Kültz, D., Daniel, P., Chang, D. P. Y., Gee, S. J., and Hammock, B.D. 2008. In vitro biological activities of the antimicrobials triclocarban, its analogues, and triclosan in bioassay screens: receptor-based bioassay screens. Environ. Health Perspect. doi:10.1289/ehp.11200, online 16 May 2008.
Chen, J., Ahn, K. C., Gee, N. A., Ahmed, M. I., Duleba, A. J., Zhao, L., Gee, S. J., Hammock, B. D., and Lasley, B.L. 2008. Triclocarban enhances testosterone action: a new type of endocrine disruptor? Endocrinology. 149(3):1173-9.
- ^Aiello, A. E., Larson, E. L., and Levy, S. B. 2007. Consumer antibacterial soaps: effective or just risky? Clin Infect Dis. 45(2):137-47.
Tan, L., Nielsen, N. H., Young, D. C., and Trizna, Z.; Council on Scientific Affairs, American Medical Association. 2002. Use of antimicrobial agents in consumer products. Arch. Dermatol. 138(8):1082-6.
- ^Aiello, A. E., Marshall, B., Levy, S. B., Della-Latta, P., Lin, S. X., and Larson, E. 2005. Antibacterial cleaning products and drug resistance. Emerg. Infect. Dis. 11(10):1565-70.
Jang, H. J., Chang, M. W., Toghrol, F., and Bentley, W. E. 2008. Microarray analysis of toxicogenomic effects of triclosan on Staphylococcus aureus. Appl. Microbiol. Biotechnol. Jan 22 [Epub ahead of print].
Schweizer, H. P. 2001. Triclosan: a widely used biocide and its link to antibiotics. FEMS Microbiol Lett. 202(1):1-7.
Webber, M. A., Coldham, N.G., Woodward, M. J., and Piddock, L. J. V. 2008. Proteomic analysis of triclosan resistance in Salmonella enterica serovar Typhimurium. Journal of Antimicrobial Chemotherapy. 62:92-97
Webber, M. A., Randall, L. P., Cooles, S., Woodward, M. J., and Piddock, L. J. V. 2008. Triclosan resistance in Salmonella enterica serovar Typhimurium. Journal of Antimicrobial Chemotherapy. 62:83–91.
- ^U.S. Environmental Protection Agency. What are Antimicrobial Pesticides?