Hypothesis-driven weight-of-evidence analysis of endocrine disruption potential: a case study with triclosan

Abstract

Triclosan is an antimicrobial agent used in a range of consumer products, such as deodorants, oral care, clothing, and household items. As with many consumer products, triclosan can be rinsed down the drain and transported to wastewater treatment plants. While most is eliminated during activated sludge sewage treatment by biodegradation and adsorption, some triclosan enters the aquatic environment and may expose wildlife. Given the potential for exposure to both humans and wildlife, resolving whether triclosan is endocrine active is important due to growing concerns about potential adverse public health and environmental effects of endocrine-disrupting substances. A weight of evidence (WoE) analysis focusing on specific hypotheses related to interaction with estrogen, androgen, and thyroid hormone pathways, and steroidogenesis was applied to triclosan. This WoE procedure involved systematic consideration of each endpoint, focused on screening level studies in the US Endocrine Disruptor Screening Program, as well as those in levels 1 through 5 of the OECD Conceptual Framework. This was followed by a semiquantitative relevance weighting of each endpoint to a given hypothesis to reach scientifically justified conclusions. Use of all relevant and reliable information and consistent observations in multiple studies strengthen support for or against each mode of action hypothesis. Using data from multiple animal species and in vitro systems, this systematic and transparent WoE assessment indicated that triclosan is not acting as an agonist or antagonist within the estrogen, androgen, thyroid, or steroidogenic pathways and is not impacting endocrine pathways as a lead or primary mode of toxicity.

Keywords:

• Endocrine Disruptor Screening Program
• endocrine screening
• regulatory toxicology
• endocrine agonist
• endocrine antagonist
• estrogen
• androgen
• thyroid
• steroidogenesis
• antimicrobial
• data quality

Acknowledgements

The authors gratefully acknowledge the comments provided by six reviewers selected by the Editor and anonymous to the authors. The comments were helpful to the authors in revising the paper.

Declaration of interest

The employment affiliation of the authors is as shown on the cover page. Dr Ellen Mihaich is the owner of Environmental and Regulatory Resources, a private consulting firm providing services to the private and public sectors. Her work on this paper was funded by the Colgate-Palmolive Company. Colgate-Palmolive formulates consumer products with triclosan. This review paper was prepared during the normal course of employment of the authors. The authors have sole responsibility for the writing and content of this paper.