Flawed Experimental Design Reveals the Need for Guidelines Requiring Appropriate Positive Controls in Endocrine Disruption Research
A study published in Toxicological Sciences (Ryan et al., 2009) illustrates the importance of examining appropriate doses of both the positive control and the test chemical in research on endocrine-disrupting chemicals. For the three low doses of bisphenol A (BPA) that were fed to rats during pregnancy and lactation, there were no effects on female offspring (there were also no effects on male offspring from the same experiment; Howdeshell et al., 2008). A review of the results of the positive control doses makes it clear that the experiment cannot adequately assess the consequences of low-dose exposure to BPA because the animal model is insensitive to low doses of the positive control estrogen. Therefore, conclusions being drawn from this experiment about low-dose responses to any estrogen are invalid, including that of “no harm” from the low doses of BPA that were tested. However, the experiment is important because it highlights the need to apply basic principles of study design, long known and accepted in studies of hormones and hormonally active drugs, to toxicological studies of chemicals with hormonal activity.
R. Thomas Zoeller, F.S. vom Saal, B. T. Akingbemi, S. M. Belcher, D. A. Crain, D. Crews, L. C. Guidice, P. A. Hunt, C. Leranth, J. P. Myers, A. Nadal, N. Olea, V. Padmanabhan, C. S. Rosenfield, A. Schneyer, G. Schoenfelder, C. Sonnenenschein, A. M. Soto, R. W. Stahlhut, S. H. Swan, L. N. Vandenberg, H. S. Wang, C. S. Watson, and W. V. Welshons. "Flawed Experimental Design Reveals the Need for Guidelines Requiring Appropriate Positive Controls in Endocrine Disruption Research" Toxicological Sciences 115 (2010): 612-613.
Available at: http://works.bepress.com/rthomas_zoeller/1