The importance of appropriate controls, animal feed, and animal models in interpreting results from low-dose studies of bisphenol A.

Interpreting results of studies that report only negative effects is problematic. A number of published studies to determine whether chemicals with estrogenic activity can cause effects at low doses have not taken into account the possibility that the commercial animal feed being used can mask effects of even potent estrogenic drugs such as diethylstilbestrol (DES). In addition, the sensitivity of the strain of animal being used for the specific category of chemical being tested has not always been described. For environmental chemicals, such as the estrogenic polycarbonate plastic monomer bisphenol A, DES is an appropriate positive control for estrogenic effects, and using an appropriate low dose of DES can eliminate the possibility of false-negative conclusions of safety when the above or other variables contribute to the negative outcome. Only when simultaneous positive effects of low doses of a positive control chemical such as DES and negative effects of environmentally relevant low doses of the test chemical are demonstrated within the same experiment are conclusions of no effect of the test chemical warranted, and this has not been reported for bisphenol A in any study. Instead, more than 90 refereed journal publications have reported effects due to exposure to low doses of bisphenol A in a wide variety of animals (for references see: http://rcp.missouri.edu/endocrinedisruptors/vomsaal/vomsaal.html). However, due to lack of attention to the importance of appropriate positive controls, a small number of studies reporting negative effects of bisphenol A have created a false sense of controversy regarding low-dose effects of bisphenol A. Copyright 2005 Wiley-Liss, Inc.