Public concern regarding environmental hazards is perhaps greatest when potential exposures are related to fetal development, pregnancy loss and/or reproductive health. An increasing body of evidence reveals associations between various therapeutic/environmental compounds that act as endocrine disrupting substances (EDS) and many sex hormone sensitive diseases/disorders (Colborn and Clement, 1992; Guillette, 2006; Massart et al., 2006). Exposure to these EDS can result in reduced fecundity, abnormal fetal development, delayed onset of puberty, disruption of ovarian function, abnormal lactation, early onset of reproductive senescence and cancer (Sharpe and Irvine, 2004; Buck Louis et al., 2006; Darbre, 2006; Guillette, 2006; Maffini et al., 2006). These adverse effects appear to be mediated largely through their ability to interfere with sex steroid action. In some cases, the etiologies of these conditions are believed to be environmental in origin as a result of persistent contaminations (Lipworth, 1995). More importantly, EDS may pose species specific risks that are difficult to investigate because they also often act silently with severe latent adverse effects (Fenton, 2006).
A large pool of literature exists for EDS with estrogenic potential and a large number of environmental hazards with estrogenic properties have been identified and classified (Guillette, 2006). While there are similar health concerns regarding androgenic EDS that can reduce sperm production, alter genital development and contribute to neurological syndromes in males, the identification and classification of these putative health hazards have progressed slowly. Recent reports of several non-steroidal compounds that have the ability to bind and activate the androgen receptor (AR) are of particular concern because many of these xenobiotics are ubiquitous in daily life and some are present as high production volume (HPV) compounds that are manufactured or imported into the United States in millions of pounds per year. The presence of these compounds in the environment has stimulated new interest in the identification of environmental contaminants that may act as selective AR modulators (SARMs) (Yin et al., 2003; Bohl et al., 2004; Chen et al., 2005).
Preservatives and/or antimicrobial agents are commonly used in food, soap, detergent, toothpaste, disinfectant, cosmetic and pharmaceutical products (Cabana et al., 2006; Darbre, 2006; Lakeram et al., 2006). These compounds are continually produced and are rapidly becoming prevalent at detectable concentrations: 1) environmentally in ground water and soil; and 2) in human blood, breast milk, and tissue (Hovander et al., 2002; Kolpin et al., 2002; Darbre, 2006; Dayan, 2006; Heidler et al., 2006; Nakada et al., 2006; Dayan, 2007). This knowledge has lead to growing public concern over the possible impacts on human health (Daughton and Ternes, 1999; Darbre, 2006). While some of these compounds have demonstrated varying estrogenic potencies, their androgenic properties remain poorly characterized. This study investigates the androgenic potential of selected antimicrobial and preservative compounds to which humans are exposed daily. This report specifically focuses on alkyl hydroxyl benzoate (parabens), triclosan and thymol through the application of a recently developed bioassay for human AR ligands (Chen et al., 2006). This cell-based AR-mediated bioassay assesses both androgenic and antiandrogenic properties of natural and synthetic compounds and its application provides new information on potential environmental EDS. The antimicrobial and preservative agents tested in this report are small non-steroidal structures containing a phenolic moiety. The data presented demonstrate that some widely used antimicrobial compounds have antiandrogenic properties and warrant further investigation to fully understand their potential impact on human reproductive health.