2018 CLARITY study of BPA safety is substandard science & repeats previously fatal mistakes

The draft of a new study by the FDA on the safety of Bisphenol A (BPA) is a glaring example of substandard federal regulatory science that continues to place public health at risk.

The study is rife with amateurish mistakes, antiquated toxicology, and a willful blindness to obvious experimental flaws that render its data and conclusions invalid.

On February 23, Stephen Ostroff, FDA Deputy Commissioner issued a premature news release pronouncing chemical BPA (Bisphenol A) safe to consume.

The news release, which seemed calculated to bias the public discussion, was issued before peer review, before any scientific consensus, and without the substantial data from several teams of university experts. Further, the study fails to incorporate 34 appendices which are located inconveniently on a separate web page: List of Appendices. What’s more, 9 of those appendices are unavailable online and available only by a separate request.

BPA is an additive in many plastics the CDC says circulates in the bloodstream of nearly every American and which the vast majority of hundreds of well-conducted university research studies indicate can cause or contribute to obesity, Type 2 diabetes, cancer,  and other maladies.

Many of those current studies are cited among the 845 citations in this article: Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses.

 

What’s more, the current FDA study repeats the same fundamental scientific errors as a preliminary study four years ago.

Contaminated Controls: Junior-high-school lab mistake invalidates the study

The biggest junior high-school science flaw committed by the FDA study is the fact that their control animals were already contaminated with BPA.

This is important because valid experiments are about measuring the “before” and the “after.” To do this, you must have a control.

The control is the “before” — the measured state of a system (or an animal) before it is affected by the experiment (the “after”).

The control offers a valid way of measuring whether an experiment has an effect, and if so, by how much.

In this case, the FDA and its BPA-contaminated mice don’t provide a valid “before” to benchmark the “after.”

You can’t get valid data in a controlled environment if the environment is not control

Back in 2014, my collaborator, Rebecca Yeamans-Irwin and I pointed out the very same mistake by the very same key FDA study authors and recommended at the time that their paper should have been retracted. It was not retracted and is one of the footnote citations in this newly released draft that follows the same structure.

The fatal flaw of contaminated controls is aggravated by the failure of this, and the previous study, to measure BPA serum levels in test animals.

Among the other serious scientific mistakes repeated in this study include:

  • Improper feeding method (oral gavage ) fails to recreate appropriate BPA Absorption and introduces non-chemical stressors. Oral gavage forces a dose directly into the esophagus of test animals. In normal food consumption, BPA and many other substances are absorbed by gums and the mucosal tissue of the oral cavity and transfer directly into the bloodstream. Other amounts of BPA are digested and metabolized in different ways.
  • Not only  does oral gavage distort the measurement of BPA level,  but it is a stressor that could affect the test animal and study outcomes
  • Use of a Rat Strain that is notoriously resistant to BPA and other endocrine disruptors

So, why not humans?

All of this begs the question: If BPA is so safe, why not test it on humans? After all, the fact that mice are not humans is a substantial reason why many pharmaceuticals that show great promise in mice fail miserably in human trials.

The reason is that Institutional Review Boards/Committees on Human Research at American universities and research institutions accept the conclusion that BPA is harmful as indicated by the vast majority of all studies on it. Even a diet-replacement study using foods readily available at the supermarket requires a  university medical school Approval letter

Uncontaminated human controls rare

Even if BPA was considered safe by the scientific establishment, finding uncontaminated human controls is nearly impossible. For that reason, newer, more precise methods must be developed.

FDA study methods stuck in a bygone state of mind

New methods are an anathema to federal regulators. Just as buggy whips and 300-baud modems still have a use in the under-developed hinterlands of Third World countries, so too do some of the techniques demanded today by the FDA.

The following are GLP toxicological techniques used in this latest study that can still be useful for long-established assessment of health problems such as acute poisoning or those which can be observed with the naked eye or standard optical microscope techniques.

Organ dissection that assesses:

  • wet weight changes of tissues,
  • gross histologic changes (easily seen tissue changes) such as tumors or other visible abnormalities and,
  • developmental landmarks such as vaginal opening and ano-genital distances

In other words, if it can’t be seen with the naked eye, measured with a ruler or a balance scale or observed with a standard optical microscope using preparation techniques developed more than 60 years ago, then it does not exist for old-line toxicologist practitioners of GLP.

It is vital to understand that those were most everything that toxicologists knew how to do up until the last 15 or 20 years.

Equally significant, that older era of toxicologists were taught that every chemical had a fixed toxic threshold and was harmless below that level. These were the toxicologists and chemists from an era whose mantra was “the solution to pollution is dilution.”

Hormone disrupting chemicals have destroyed all that. Many old-line toxicologists simply cannot come to grips with this new world. For more, see: Old Ideas, Old Science Cripple Federal Regulation.

Modern science uses precision toxicology

Chemical trade organizations and manufacturers rely exclusively upon traditional risk assessments and declare that BPA is unequivocally safe (Facts about BPA).

Those safety claims are made despite hundreds of current, published, peer-reviewed, university, and medical studies to the contrary.

This extensive piece on science regulation from the Boston University School of Law, explores in detail why traditional methods — but not more current academic science — dominate the U.S. regulatory process: “Equal Treatment for Regulatory Science.”

Using modern toxicology

Pharmaceutical companies know that more precise methods dealing with molecular pathways and genetics are needed and are among the leaders in developing those.

Significantly, environmental chemicals like BPA can adversely affect the same mechanisms as therapeutic compounds. For a recent example, see: Heat Shock Protein Hsp27 points to causal link between BPA and cancer & chemotherapy resistance.

As another example, BPA has been found to increase the production of a particular protein known as CDK5. As it happens, published studies show that increasing cdk5 production is a key factor in medullary thyroid cancer as well as Alzheimer’s disease.

Using the cellular, genetic and and molecular mechanisms that underpin approved pharmaceuticals means that direct human trials on environmental chemical risks are available and have already done — by proxy — by drug investigators.

 

 

 

 

 

 

 

 

 

 

Perhaps it is a simple error of poor government organization, but a complete set of documents pertaining to the study are frustratingly hard to assemble.

 

Supplemental Appendices

List of Appendices

 

April 26, 2018 Peer Review of the Draft NTP Research Report on the CLARITY-BPA Core Study

One red flag in studies gets raised when the investigators cite their own seudies.10 of the 51 sources cited are from Delaclos.

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