Scientifically unfounded precaution drives European
Commission’s recommendations on EDC regulation, while defying common sense, well-established science and risk assessment principles
We, the undersigned editors of prominent journals of
pharmacology and toxicology, are drawing your attention to the imminent decisions by the European Commission to enforce a regulatory framework for so-called endocrine disrupting chemicals (EDCs). The currently drafted framework is based on virtually complete ignorance of all well-established and taught principles of pharmacology and toxicology, of opinions raised by the European Commission’s own competent expert authority (European Food Safety Authority (EFSA, 2013)), and of critical statements made by member countries, while avoiding asking for support from the European Commission’s own scientific expert committees.
As a statement, and as emphasized by others before, “endocrine disruption” is not a toxicologically defined endpoint but a mode-of-action that may or may not result in adverse effects. In itself, the mode-of-action concept implies the necessary existence of a threshold as experimentally proven for numerous other non-genotoxic agents including EDC’s.
Moreover, endocrine systems play a fundamental role in the physiological response to changes in the
environment with the aim of keeping an organism’s biology within the homeostatic space. It is the task of toxicologists to make the distinction between those effects that are within this adaptive range and effects that go beyond the boundaries of this space and thus can be called adverse. Such adverse effects can be observed in adequately designed and performed toxicity studies…full 2013 open letter here (pdf file)
See alsoenvironment with the aim of keeping an organism’s biology within the homeostatic space. It is the task of toxicologists to make the distinction between those effects that are within this adaptive range and effects that go beyond the boundaries of this space and thus can be called adverse. Such adverse effects can be observed in adequately designed and performed toxicity studies…full 2013 open letter here (pdf file)
- Inconvenient Toxicology Truths Part 1. Endocrine disrupters -- A prime example of the "cherchez la femme!" fallacy.
- European Science Under Siege /COSMOS Magazine
- Weight-of-Evidence Evaluation of Reproductive and Developmental Effects of Low Doses of Bisphenol A Crit Reviews in Toxicology January 2009, Vol. 39, No. 1 , Pages 1-75 Julie E. Goodman, Raphael J. Witorsch, Ernest E. McConnell, I. Glenn Sipes, Tracey M. Slayton, Carrie J. Yu, Amber M. Franz, and Lorenz R. Rhomberg
Conclusion from Goodman et al 2009:
Overall, our conclusions on specific endpoints, and on the weight of evidence for low-dose effects in rodents in general, are consistent with the two previous reviews (Goodman et al., 2006; Gray et al., 2004a); although some statistically significant findings in rodents exist at BPA doses ≤ 5 mg/kg -d, they are generally countered by more numerous studies showing no effect for similar reproductive and developmental endpoints. No effect is marked or consistent across studies, doses, or time points.
If there were a true hormonal disruption by very low doses of BPA on the development and function of the reproductive system, particular effects should occur with some regularity across studies, subject only to the power of individual studies to detect the effects and the usual vagaries of practical experiments. Any such effects should also show some intelligible and repeatable dose-response pattern (even if not a monotonic one). In fact, however, such regularities are not seen. The responses of positive controls show that sufficient doses of endogenous estrogens are indeed capable of causing the kinds of changes examined in these experiments, but even for these undoubtedly active compounds, there are doses below which alterations are not found. If very low doses of BPA are indeed estrogenic (or anti-androgenic), then the changes caused should be consistent with such a mechanism—consistent both individually (i.e., each change is similar to one that an estrogen should bring about) and as a suite of effects (i.e., all of the aspects that an estrogen is expected to affect are affected). In fact, many of the putative effects are opposite what one would expect as the impact of such a mode of action, and in most cases, the suite of effects that would be expected is not consistently produced. Finally, gene expression arrays fail to show very low doses of BPA altering gene expression patterns, leaving in question the plausibility of action by a hormonal-control perturbation, which would be expected to alter gene expression patterns in a way similar to endogenous hormones.
In view of these factors, we find little scientific support for the assertion that very low oral doses of BPA (≤ 5 mg/kg -d, orders of magnitude higher than typical human exposure) are capable of disrupting the development or functioning of the reproductive system in people in the general population.
Overall, our conclusions on specific endpoints, and on the weight of evidence for low-dose effects in rodents in general, are consistent with the two previous reviews (Goodman et al., 2006; Gray et al., 2004a); although some statistically significant findings in rodents exist at BPA doses ≤ 5 mg/kg -d, they are generally countered by more numerous studies showing no effect for similar reproductive and developmental endpoints. No effect is marked or consistent across studies, doses, or time points.
If there were a true hormonal disruption by very low doses of BPA on the development and function of the reproductive system, particular effects should occur with some regularity across studies, subject only to the power of individual studies to detect the effects and the usual vagaries of practical experiments. Any such effects should also show some intelligible and repeatable dose-response pattern (even if not a monotonic one). In fact, however, such regularities are not seen. The responses of positive controls show that sufficient doses of endogenous estrogens are indeed capable of causing the kinds of changes examined in these experiments, but even for these undoubtedly active compounds, there are doses below which alterations are not found. If very low doses of BPA are indeed estrogenic (or anti-androgenic), then the changes caused should be consistent with such a mechanism—consistent both individually (i.e., each change is similar to one that an estrogen should bring about) and as a suite of effects (i.e., all of the aspects that an estrogen is expected to affect are affected). In fact, many of the putative effects are opposite what one would expect as the impact of such a mode of action, and in most cases, the suite of effects that would be expected is not consistently produced. Finally, gene expression arrays fail to show very low doses of BPA altering gene expression patterns, leaving in question the plausibility of action by a hormonal-control perturbation, which would be expected to alter gene expression patterns in a way similar to endogenous hormones.
In view of these factors, we find little scientific support for the assertion that very low oral doses of BPA (≤ 5 mg/kg -d, orders of magnitude higher than typical human exposure) are capable of disrupting the development or functioning of the reproductive system in people in the general population.
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