Sunday, June 29, 2014

Low-Dose BPA Paper In Toxicological Sciences Fatally Flawed & Should Be Retracted: Plagued By Massive Errors & Poor Design. Contaminated Controls Raise Issues About Federal Breeding Colony Integrity

By Lewis Perdue and Rebecca L. Yeamans (Corresponding author:
NOTE: An earlier version of this paper originally appeared on on Feb., 24, 2014.
This version is enormously expanded to address peer-review suggestions from multiple prominent researchers. Those who helped improve this paper who wish to remain un-named because the direct and un-nuanced data and opinions expressed here may cause funding, political or other undesirable issues.
However, we are enormously grateful for their help, assistance and encouragement.

Please click this link for a .pdf version of this post.
Bisphenol A (BPA) has become nearly ubiquitous in our environment and can be found in many different products, including the plastic in water bottles and baby bottles, thermal paper for printers, and even in dental sealants and medical devices including intravenous fluid and chemotherapy bags and tubing(26,27,28,29,30,31).
Thousands of studies have been published that examine the levels of BPA and other endocrine disruptors present in the environment along with the mechanisms and pathways those chemicals may take to affect or harm living things.There is, however, considerable controversy concerning negative health effects of so-called “low-dose” exposures.
One recent study, published in the journal Toxicological Sciences, stated as its goals the desire to help shed light on the conflicting body of evidence. Unfortunately, that study, "Toxicity Evaluation of Bisphenol A Administered by Gavage to SPRAGUE-DAWLEY Rats from Gestation Day 6 through Postnatal Day 90(1)"is fatally flawed.
The study(1) by Delclos et al., concluded that low-dose BPA is not harmful. However, that conclusion cannot be scientifically justified by the experiment as conducted. This study suffers from numerous and massive errors including; by the eventual admission of the authors(1); the violation of one of the scientific method’s paramount experimental rules: the control subjects were contaminated by the chemical substance being evaluated.
Additionally, while the study authors claim to have no idea of the BPA contamination source(1), an examination of the paper and a current understanding of the science indicate numerous avenues of contamination that are obvious, well-established, and should have been considered in any careful experiment design and conduct.
This letter will explore a number of those sources and their consequences in more detail below, but it merits consideration at this stage that one possible contamination source could jeopardize results of experiments underway in the very substantial, multi-agency program known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA).

Test Animal Contamination Concern For CLARITY-BPA
Delclos et al. state that the test animals in their experiment were obtained from the NTP breeding colony(1). If so, then their contaminated controls may also hold significance for the scores of investigators participating CLARITY-BPA.
“CLARITY-BPA is a collaborative effort between NTP and NIEHS with support from FDA to conduct a perinatal 2-year guide- line chronic rodent toxicity study on BPA(95).”
The program is designed to investigate “scientific uncertainties about BPA’s health effects to better inform regulatory decision-making. …The CLARITY-BPA consortium is made up of NCTR staff, NIEHS and NTP staff, and 12 extramural grantees(95).”
The core guideline- compliant study is being conducted at FDA’s National Center for Toxicological Research (NCTR) CLARITY-BPA investigators, both with government at universities, must use rats from the NTP breeding colony(95).”
The unknown source of the BPA contamination of controls raises the issue of whether the animals in the NTP breeding colony are regularly monitored for BPA and other endocrine disruptors.
Ongoing and regular population sampling by NTP would alert breeders to potential contamination. Prior to release, batch samplings would assure the receiving investigators of the purity of their test animals.
It is unknown whether the NTP breeding colony has monitoring protocols in place that adequately monitor test animals and assure investigators that the test subjects are uncontaminated and appropriate for experimentation.
Avoidable Errors Accumulate
In addition to the contamination error, the study fails on an accumulation of other serious errors:
  • Potential contamination by other endocrine-disrupting compounds
  • Unknown Combination Effects Of Stressors
  • Use of oral gavage which introduces non-chemical stressors
  • Use of oral gavage which fails to recreate appropriate BPA Absorption
  • Inappropriate Rat Strain
  • Poor choice of outcome measures
  • Failure to use current science in BPA and Endocrine Disruptor Compound (EDC) research
  • Erroneous claim that BPA is “weak” estrogen
  • Failure to identify well-known exogenous source(s) of BPA contamination
  • Failure to identify well-known exogenous source(s) and estrogenic activity of equipment and supplies
  • Failure to measure BPA levels in any of the animals except in the test cohort at the end of the trial
  • Failure to measure other exogenous estrogenic compounds in test animals
  • Use of oral gavage
  • Wrongly examining toxicity when timing is a bigger issue
  • Failure to include disclosure of conflicts