Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A

Environ Res. 2006 Jan;100(1):50-76. doi: 10.1016/j.envres.2005.09.001. Epub 2005 Oct 27.


Over six-billion pounds per year of the monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, resins lining cans, dental sealants, and polyvinyl chloride plastic products. There are 109 published studies as of July 2005 that report significant effects of low doses of BPA in experimental animals, with many adverse effects occurring at blood levels in animals within and below average blood levels in humans; 40 studies report effects below the current reference dose of 50 microg/kg/day that is still assumed to be safe by the US-FDA and US-EPA in complete disregard of the published findings. The extensive list of significant findings from government-funded studies is compared to the 11 published studies that were funded by the chemical industry, 100% of which conclude that BPA causes no significant effects. We discuss the importance of appropriate controls in toxicological research and that positive controls are required to determine whether conclusions from experiments that report no significant effects are valid or false.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Diethylstilbestrol / toxicity
  • Environmental Pollutants / toxicity*
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Humans
  • Male
  • Phenols / toxicity*
  • Research Design*
  • Risk Assessment
  • Toxicity Tests / methods*
  • United States
  • United States Environmental Protection Agency
  • United States Food and Drug Administration


  • Benzhydryl Compounds
  • Environmental Pollutants
  • Estrogens, Non-Steroidal
  • Phenols
  • Diethylstilbestrol
  • bisphenol A