Abstract
Triclosan is a widely used antimicrobial agent in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive lifetime exposures to triclosan, yet data on the chronic dermal toxicity/carcinogenicity of triclosan are still lacking. We evaluated the toxicity/carcinogenicity of triclosan administered dermally to B6C3F1 mice for 104 weeks. Groups of 48 male and 48 female B6C3F1 mice received dermal applications of 0, 1.25, 2.7, 5.8, or 12.5 mg triclosan/kg body weight (bw)/day in 95% ethanol, 7 days/week for 104 weeks. Vehicle control animals received 95% ethanol only; untreated, naïve control mice did not receive any treatment. There were no significant differences in survival among the groups. The highest dose of triclosan significantly decreased the body weight of mice in both sexes, but the decrease was ≤ 9%. Minimal-to-mild epidermal hyperplasia, suppurative inflammation (males only), and ulceration (males only) were observed at the application site in the treated groups, with the highest incidence occurring in the 12.5 mg triclosan/kg bw/day group. No tumors were identified at the application site. Female mice had a positive trend in the incidence of pancreatic islet adenoma. In male mice, there were positive trends in the incidences of hepatocellular carcinoma and hepatocellular adenoma or carcinoma (combined), with the increase of carcinoma being significant in the 5.8 and 12.5 mg/kg/day groups and the increase in hepatocellular adenoma or carcinoma (combined) being significant in the 2.7, 5.8, and 12.5 mg/kg/day groups.
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The data that support the findings of this study are available from the corresponding author, upon request.
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Acknowledgements
We are indebted to Wafa A. Harrouk, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, for excellent advice during this study. We thank Patricia Shores, Andy Matson, and Mark Moore for providing dose formulations, animal diets, and animal care; and Matthew Bryant, Gonçalo Gamboa da Costa, and Mani Chidambaram for assessing the identity and purity of the triclosan and vehicle as well as conducting dose stability and certification analyses.
Funding
This study was funded by an Interagency Agreement between the US Food and Drug Administration (FDA) and the US National Institute of Environmental Health Sciences (NIEHS) (FDA IAG #224-17-0502 and NIEHS IAG #AES12013). This manuscript was reviewed in accordance with FDA procedures prior to submission. This manuscript reflects the views of the authors and does not necessarily reflect those of the FDA or the NIEHS.
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Fang, JL., Vanlandingham, M.M., Olson, G.R. et al. Two-year dermal carcinogenicity bioassay of triclosan in B6C3F1 mice. Arch Toxicol 98, 335–345 (2024). https://doi.org/10.1007/s00204-023-03613-1
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DOI: https://doi.org/10.1007/s00204-023-03613-1