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deBriefings risk" (Sheehan, 1998b). It should also be noted that the claim on p. 62978 that soy protein foods are GRAS [Generally Recognized As Safe] is in conflict with the recent return by CFSAN [Center for Food Safety and Applied Nutrition, FDA] to Archer Daniels Midland of a petition for GRAS status for soy protein because of deficiencies in reporting adverse effects in the petition. Thus GRAS status has not been granted. Linda Kahl can provide you with details. It would seem appropriate for FDA to speak with a single voice regarding soy protein isolate. Taken together, the findings presented here are self-consistent and demonstrate that genistein and other isoflavones can have adverse effects in a variety of species, including humans. Animal studies are the front line in evaluating toxicity as they predict, with good accuracy, adverse effects in humans. For the isoflavones, we additionally have evidence of two types of adverse effects in humans, despite the very few studies that have addressed this subject. While isoflavones may have beneficial effects at some ages or circumstances, this cannot be assumed to be true at all ages. Isoflavones are like other estrogens in that they are two-edged swords, conferring both benefits and risk (Sheehan and Medlock, 1995; Sheehan, 1997). The health labeling of soy protein isolate for foods needs to be considered just as would the addition of any estrogen or goitrogen to foods, which are bad ideas. Estrogenic and goitrogenic drugs are regulated by FDA, and are taken under a physician's care. Patients are informed of risks, and are monitored by their physicians for evidence of toxicity. There are no similar safeguards in place for foods, so the public will be put at potential risk from soy isoflavones in soy protein isolate without adequate warning and information. Finally, NCTR is currently conducting a long-term multigen- eration study of genistein administered in feed to rats. The analysis of the dose-range-finding studies are near-complete or complete now. As preliminary data, which is still confidential, may be relevant to your decision, | suggest you contact Dr Barry Delclos at the address on the letterhead, or e-mail him. Sincerely, Daniel M. Sheehan Daniel R. Doerge Enclosures cc: Dr Bernard Schwetz, Director, NCTR cc: Dr Barry Delclos References Biol. Med. 217:247-253, 1998. * Sheehan, D.M., "Herbal medicines and phyto- * Cassidy, A., Bingham, S. and Setchell, ¢ Ishizuki, Y., Hirooka, Y., Murata, Y. and estrogens: risk-benefit considerations", Proc. K.DR., "Biological effects of soy protein rich Togasho, K., "The effects on the thyroid gland Soc. Exp. Biol. 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