Hindawi Publishing Corporation Journal of Toxicology Volume 2009, Article ID 307618, 13 pages doi:10.1155/2009/307618 Research Article Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient Ray A. Matulka,1 Ikuo Matsuura,2 Tohru Uesugi,3 Tomomi Ueno,4 and George Burdock1 1 Burdock Group, Orlando, FL 32801, USA 2 The Safety Assessment Division II, Mitsubishi Chemical Safety Institute Ltd., Tokyo 105-0014, Japan 3 The Department of Toxicology, Otsuka Pharmaceutical Co. Ltd., Tokushima 771-0192, Japan 4 The Saga Nutraceuticals Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima 771-0192, Japan Correspondence should be addressed to Ray A. Matulka, rmatulka@burdockgroup.com Received 29 May 2008; Revised 7 August 2008; Accepted 7 October 2008 Recommended by Robert Tanguay Consumption of the isoﬂavones daidzein, genistein, glycitein, and their structural analogues is generally considered beneﬁcial to human health. Equol is not found in soy, but is converted from daidzein by human gut bacterial ﬂora. Research indicates that between 30–50% of the population is capable of converting daidzein to equol; therefore, there has been recent development of a new equol-rich functional food that relies on bacterial conversion of daidzein to equol under strictly controlled conditions. Therefore, a new equol-rich soy product (SE5-OH) has been developed, based on the bacterial conversion of daidzein; and its reproductive and developmental toxicity has been evaluated in a two-generation study and a developmental toxicity study with Sprague-Dawley rats at dose levels of 200, 1000, and 2000 mg/kg/day by gavage. SE5-OH contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein, and 0.30% glycitein. From the reproductive study, the no-observed-adverse-eﬀect-level (NOAEL) for SE5-OH determined for both male and female rats is 1000 mg/kg/day (6.5 mg equol/kg/day). In the developmental toxicity phase of the study, no eﬀects by SE5-OH were found in the embryo-fetus at any of the doses tested. The NOAEL for developmental eﬀects of SE5-OH is 2000 mg/kg/day (13 mg equol/kg/day). Copyright © 2009 Ray A. Matulka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction Over the past two decades, scientiﬁc literature has indi- cated that consumption of soy products and, in particular, their isoﬂavone components have been associated with the reduction of the risk of cancer, coronary vascular disease, osteoporosis, and other pathologies that are associated with menopause and ageing in both sexes [1–3]. One such isoﬂavone is equol: a microbial metabolite of daidzein, which is structurally related to 17β-estradiol [4]. Consumption of daidzein in subjects that were found to be able to metabolize daidzein to equol has been linked with delay in the onset of menopause and menopausal-associated symptoms, markers of cardiovascular disease, and prostate cancer [5, 6]; however, there is conﬂicting evidence concerning the ability to pro- duce equol and subsequent health beneﬁts [6, 7]. Although there are known dietary sources of equol, the levels of equol in these milk samples are relatively low (in the range of 60–450 ng equol/mL) [8, 9]. Therefore, the consumption of equol-enriched soy-based products may be of health beneﬁt to individuals who do not convert daidzein to equol. In nature, equol is formed exclusively by the intestinal microbiota although chemical synthesis pathways have also been described [10, 11]. The enzymatic process of producing equol from daidzein resides with the gut microbial ﬂora [12, 13], similar to the pathway presented in Figure 1. Although it has been estimated that there are more than 400 species of bacteria in the human gut that may inﬂuence the normal structure and function of the intestinal system [14, 15], research indicates that, depending upon the population studied, between 30–50% of the population is host to bacteria which metabolize daidzein into equol [6, 16, 17]. Recent research has indicated that humans that host bacteria, able to metabolize daidzein to equol, convert approximately 30–40% of daidzein into equol, and the types of food consumed may be one of several factors that aﬀect the ability