Superfund Research Program
Assessing the Adverse Effects of Environmental Hazards on Reproductive Health
Project Leader: Bill L. Lasley
Grant Number: P42ES004699
Funding Period: 1995-2015
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Final Progress Reports
This year Dr. Lasley and his research team investigated the potential broad adverse effects of small molecules such as the antimicrobial triclocarban (TCC) that is found in some bar soaps. They had previously shown a specific effect of TCC on modulating the signal transduction of multiple steroid hormones acting in conjunction with their cognate nuclear receptor. These in vitro studies revealed consistent and strong in vitro effects with several steroid/receptor pairs. In addition, these effects were confirmed with in vivo studies in regard to testosterone. This year the researchers investigated non-steroid signal transduction pathways using the rat animal model exposed to TCC ad lib in the diet. In this regard the research team found that TCC alone stimulates CYP1A1 and MCP-1 mRNA expression in the rat lung and that these responses are to a lesser degree when TCC is with combined with the inflammatory agent, budesonide. In addition TCC alone attenuate the negative effect of budesonide on COX-1 mRNA expression and this reversal is greater when TCC is combined with budesonide. These new data support the concept that TCC has "cross-talk" capabilities with the estrogen receptor (ER) and the dioxin receptor (AhR) regulons. These unexpected results raise the question of why more profound and consistent effects are not seen when humans are exposed daily to TCC. An in vivo study with young girls documented that circulating levels of TCC that are thought to be effective over the time-course of less than an hour after a whole body, normal shower (see update last year). The researchers' current hypothesis is that in humans, prior exposures to agents that increase catabolic enzymes such as CYP1A1 and the short exposure time interval in real-world human exposure such as showering, act together to reduce the half-live of TCC to an effective exposure time period that is insufficient to elicit adverse effects. Additional in vitro time course studies indicated that there is a 2-4 hour minimal time exposure requirement for TCC to induce some effects such as augmentation of steroid hormone signaling. Taken together, these results suggest that some in vivo studies, such as exposure by gastric lavage, may not always produce positive results because the effective exposure period is too short. The researchers now posit that unless the exposure to TCC is prolonged, as in dietary exposures as they have demonstrated repeatedly with the rat animal model, the short half-live of TCC may attenuate and possibly prevent adverse reactions.