Bisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, the resin lining of cans, and other products, with global capacity in excess of 6.4 billion lb/year. Because the ester bonds in these BPA-based polymers are subject to hydrolysis, leaching of BPA has led to widespread human exposure. A recent report prepared by the Harvard Center for Risk Analysis and funded by the American Plastics Council concluded that evidence for low-dose effects of BPA is weak on the basis of a review of only 19 studies; the report was issued after a delay of 2.5 years. A current comprehensive review of the literature reveals that the opposite is true. As of December 2004, there were 115 published in vivo studies concerning low-dose effects of BPA, and 94 of these report significant effects. In 31 publications with vertebrate and invertebrate animals, significant effects occurred below the predicted "safe" or reference dose of 50 µg/kg/day BPA. An estrogenic mode of action of BPA is confirmed by in vitro experiments, which describe disruption of cell function at 10 -12 M or 0.23 ppt. Nonetheless, chemical manufacturers continue to discount these published findings because no industry-funded studies have reported significant effects of low doses of BPA, although > 90% of government-funded studies have reported significant effects. Some industry-funded studies have ignored the results of positive controls, and many studies reporting no significant effects used a strain of rat that is inappropriate for the study of estrogenic responses. We propose that a new risk assessment for BPA is needed based on a) the extensive new literature reporting adverse effects in animals at doses below the current reference dose; b) the high rate of leaching of BPA from food and beverage containers, leading to widespread human exposure; c) reports that the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice; and d) recent epidemiologic evidence that BPA is related to disease in women.

Although the beneficial effects of dietary soybean protein compared with animal proteins on plasma lipids, lipoproteins and atherosclerosis have been known for about 50 years, it has been uncertain whether these effects are due to its amino acid concentrations or other components in soybeans. To assess the effect of soybean protein's alcohol-extractable components (including the isoflavonic phytoestrogens genistein and daidzein) on plasma lipid and lipoprotein concentrations and to establish its lack of effect on the reproductive system, we fed 27 peripubertal male and female rhesus monkeys moderately atherogenic diets in which the source of dietary protein was a soy isolate (20% by weight), either containing phytoestrogens (also termed isoflavones) or with the phytoestrogens removed by alcohol extraction. The study was a crossover design with each period lasting for 6 mo. The phytoestrogen-intact soy protein (compared with the alcohol-extracted soy protein) had favorable effects on plasma lipid and lipoprotein concentrations, specifically by significantly reducing LDL+VLDL cholesterol concentrations in both males and females (approximately 30-40% lower), significantly increasing high density lipoprotein cholesterol (HDLC) concentrations for females (approximately 15% higher) and significantly lowering total plasma cholesterol (TPC):HDLC ratios (approximately 20% lower for males and 50% lower for females). The phytoestrogens had no adverse effects on the reproductive systems of either the males or females, as evaluated by reproductive hormone concentrations and organ weights at necropsy. Thus, the isoflavones in soy protein improve cardiovascular disease risk factors without apparent deleterious effects on the reproductive system of peripubertal rhesus monkeys.