Exploration of the endocrine disrupting effects of triclocarban

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): The recent finding that triclocarban (TCC) has novel endocrine disruptor (ED) properties raises the possibility that daily exposures to personal care products containing TCC could have, or may have already had, adverse health effects in humans. In vitro studies as well as preliminary in vivo studies demonstrate that TCC can act to augment the biological effect of circulating testosterone and change the morphology of accessory sex organs in male rats including the prostate gland. The probability of specific adverse human health effects are indicated by the finding of in vivo adverse effects in rats and provide a compelling argument for future population-based and possibly clinical studies to be conducted. Prior to such studies, however, additional in vivo and in vitro studies are needed to provide basic information. The present proposal will address two specific aims, each with hypothesis driven in vitro and/or in vivo studies. TCC's potential mechanism(s) of action is pursued with human cell lines while its tumorigenic potential will be evaluated using well-defined cell lines and an immunodeficient mouse animal model. In vitro studies using human prostate cell lines will better define the mechanism(s) of action of TCC at the intracellular level. The first specific aim will investigate how TCC stimulates cell proliferation and the secretion of prostate specific protein in prostate epithelial cells. The second specific aim will characterize the change in expression, stability and translocation of the androgen receptor (AR) and will investigate key AR co-activators. The expected results obtained from these proposed studies will provide future investigators with both the basic information and methodologies to investigate TCC and provide insight into the potential health risks from exposures to TCC and related compounds on prostate disease. These studies will provide the first in depth data regarding the effect and mode of action of TCC on human prostate function and development. PUBLIC HEALTH RELEVANCE: The recent finding that triclocarban (TCC) has novel endocrine disruptor (ED) properties raises the possibility that daily exposures to personal care products containing TCC could have, or may have already had, a wide range of adverse health effects in humans. Animal studies indicate the prostate gland is enlarged by TCC's toxic effects and suggests a similar adverse effect on the human prostate. The proposed studies will provide information and guide future population-based or clinical studies to investigate the health risks from exposures to TCC and related compounds in both household products and the environment.