Human dietary studies and interventions most often fail to provide consistent, human-relevant causal results. There is no consistent set of protocols and lab standards for conducting these trials with te results that
This chaos and inconsistency leads one substantial study (Carra, p.9) to declare: “With this type of data, it is difficult to draw a meaningful, intellectually honest conclusion.”
Significantly,a search of the scientific literature failed to locate controlled clinical direct human studies measuring clinically significant health effects of low-level Plastic-Derived Chemical (PDC) contamination. However, a literature search did reveal a handful of investigations in which human test subjects were directly administered Bisphenol A in order to assess BPA pharmacokinetics (but not health effects).
- Thayer KA, Doerge DR, Hunt D, et al. Pharmacokinetics of bisphenol A in humans following a single oral administration. Environ Int. 2015;83:107‐115. doi:10.1016/j.envint.2015.06.008
- Wolfgang Völkel Thomas Colnot György A. Csanády Johannes G. Filser Wolfgang Dekant, Metabolism and Kinetics of Bisphenol A in Humans at Low Doses Following Oral Administration, Chem. Res. Toxicol. 2002, 15, 10, 1281-1287 Publication Date:September 24, 2002 https://doi.org/10.1021/tx025548t
Compounding that lack of health-effects knowledge, human dietary intervention studies published so far on BPA and other plastic chemicals have focused only measuring levels of marker chemicals and have not measured direct, clinically relevant health outcome indicators.
- Rudel, R.A., Gray, J.M., Engel, C.L., Rawsthorne, T.W., Dodson, R.E., Ackerman, J.M., Rizzo, J., Nudelman, J.L., and Brody, J.G. 2011. Food packaging and Bisphenol A and Bis(2-Ethyhexyl) Phthalate exposure: Findings from a dietary intervention. Environmental Health Perspectives 119(7): 914-920.
- Sathyanarayana, S., Alcedo, G., Saelens, B.E., Zhou, C., Dills, R.L., Yu, J., and Lanphear, B. 2013. Unexpected results in a randomized dietary trial to reduce phthalate and bisphenol exposures. Journal of Exposure Science & Environmental Epidemiology 23: 378-384.
- Hutter, K.P., Kundi, M., Hohenblum, P., Scharf, S., Shelton, J.F., Piegler, K., and Wallner, P. 2016. Life without plastic: A family experiment and biomonitoring study. Environmental Research 150: 639-644.
- Ji, K., Lim Kho, Y., Park, Y., and Choi, K. 2010. Influence of a five-day vegetarian diet on urinary levels of antibiotics and phthalate metabolites: a pilot study with “Temple Stay” participants. Environmental Research 110(4): 375-382.
- Galloway, T.S., Baglin, N., Lee, B.P., Kocur, A.L., Shepherd, M.H., Steele, A.M., BPA Schools Study Consortium, and Harries, L.W. 2018. An engaged research study to assess the effect of a “real-world” dietary intervention on urinary bisphenol A (BPA) levels in teenagers. BMJ Open 8: e018742.
Extrapolation of human health effects from murine model mostly fails and creates controversy
The absence of clinically relevant human studies required that human health outcome conclusions require extrapolation from murine models.
However, no clinically credible conclusions about causation can be drawn from that extrapolation because murine model results frequently fail to translate accurately to humans. This is especially the case in drug trials where up to 92% have been shown to fail in humans following successful murine results.
That situation has, in turn, contributed to an internationally divisive scientific controversy that has prevented health professionals and consumers from making scientifically valid health decisions.
On one side of the controversy are university and independent scientists who contend that hundreds of published studies indicate that micro- and pico-molar concentrations of BPA are unhealthy. Three many examples include:
-
Flaws in design, execution and interpretation limit CLARITY‐BPA’s value for risk assessments of bisphenol A. Basic Clin Pharmacol Toxicol. 2019; 125(Suppl. 3): 32– 43. https://doi.org/10.1111/bcpt.13195.
- A. C. Gore, V. A. Chappell, S. E. Fenton, J. A. Flaws, A. Nadal, G. S. Prins, J. Toppari, R. T. Zoeller, EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals, Endocrine Reviews, Volume 36, Issue 6, 1 December 2015, Pages E1–E150, https://doi.org/10.1210/er.2015-1010
- Vandenberg LN, Hunt PA, Gore AC. Endocrine disruptors and the future of toxicology testing – lessons from CLARITY-BPA. Nat Rev Endocrinol. 2019;15(6):366‐374. doi:10.1038/s41574-019-0173-y
On the other side, corporate and some federal regulatory scientists point to the recent CLARITY-BPA study whose results — they contend — demonstrated that low levels are safe.
National Toxicology Program. 2018. NTP Research Report on the CLARITY-BPA Core Study: A Perinatal and Chronic Extended-Dose-Range Study of Bisphenol A in Rats. NTP RR 9. Research Triangle Park, NC. National Toxicology Program (9): 1-221.
CLARITY-BPA and most other published studies have been based upon an in vivo murine model whose accurate extrapolation to humans is not known. As a result, the current debate centers on protocol flaws, confounding factors, sources of contamination and the finer points of how the murine studies were conducted.
CLARITY-BPA Conclusions Challenged
Further, the CLARITY-BPA study and its predecessor are plagued by serious and scientifically fatal protocol errors that invalidate any conclusions regarding human safety or health:
- BPA: have flawed analytical techniques compromised risk assessments?,Roy Gerona, Frederick S vom Saal, Patricia A Hunt,
The Lancet Diabetes & Endocrinology, Volume 8, Issue 1,2020, Pages 11-13, ISSN 2213-8587, https://doi.org/10.1016/S2213-8587(19)30381-X. - Scientists Call FDA Statement on Bisphenol A Safety Premature
- 2018 CLARITY study of BPA safety is substandard science & repeats previously fatal mistakes
- Low-Dose BPA Paper in Toxicological Sciences Fatally Flawed & Must Be Retracted. Also Raises Doubts About Integrity Of Federal Lab Animal Facility
Resistance to human dosing: Nuremberg’s legacy?
The lack of controlled-dose human studies has been attributed to a Nuremberg-based ethical reluctance to expose human to harmful substances.
- The Nuremberg Code 70 Years Later
- Human Experimentation and Research
- Beyond Nazi War Crimes Experiments: The Voluntary Consent Requirement of the Nuremberg Code at 70
- American Doctors at the Nuremberg Medical Trial
Human experimentation ethics: Industry and federal government compliance?
The Nuremberg ethical argument fails because but humans are already legally exposed to Plastic-Derived Chemicals with scores of other potentially harmful chemicals as evidenced by the National Health and Nutrition Examination Survey (NHANES) and numerous studies confirming chronic Bisphenol A levels in human serum and urine.
- No reluctance to dose humans with bisphenol
- Ryan J. Carra, It’s in Our Blood: A Critique of the FDA’s Reluctance to Regulate the Use of Bisphenol A in the Food Supply, 14 J. Health Care L. & Pol’y 153 (2011).
- NCHS Research Ethics Review Board (ERB) Approval
- 84,000 Legal Chemicals. Fewer Than 200 Tested. Only 5 Ever Banned. Here’s Where Those Numbers Come From (2014)
NHANES
- Calafat, Antonia M., Ye, X., Wong, L-Y., Reidy, J.A., and Needham, L.L. 2008. Exposure of the US population to Bisphenol A and 4-tertiary-Octylphenol: 2003-2004. Environmental Health Perspectives 116(1): 39-44.
- National Health and Nutrition Examination Survey (NHANES) DNA Specimens: Guidelines for Proposals To Use Samples and Cost Schedule
- NHANES Informed Consent
- Calafat, A.M., Longnecker, M.P., Koch, H.M., Swan, S.H., Hauser, R., Goldman, L.R., Lanphear, B.P., Rudel, R.A., Engle, S.M., Teitelbaum, S.L., Whyatt, R.M., and Wolff, M.S. 2015. Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology. Environmental Health Perspectives 123(7): A166-8
Human dosing
Wolfgang Völkel Thomas Colnot György A. Csanády Johannes G. Filser Wolfgang Dekant, Metabolism and Kinetics of Bisphenol A in Humans at Low Doses Following Oral Administration, Chem. Res. Toxicol. 2002, 15, 10, 1281-1287 Publication Date:September 24, 2002 https://doi.org/10.1021/tx025548t
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