Progress in understanding endocrine disruption requires cross-disciplinary approaches and concepts

Several journals with interests in endocrine disruption mechanisms are joining together to present the accompanying editorial by Dr Andrea Gore (Pfeiffer Endowed Chair in Pharmacology and Toxicology at Univ. of Texas-Austin, Editor-in-Chief of Endocrinology), co-signed by many like-minded and accomplished scientists. This is a response to a recent editorial by Dietrich et al. published in several toxicology-focused journals^1-3 that criticized the European Commission’s new recommendations on endocrine-disrupting chemicals.

Gore et al. have a much different take on what is “common sense” than those toxicologists signing on to Dietrich et al. We have taken into consideration principles of endocrinology that inform our understanding of the actions of compounds that imperfectly mimic hormonal ligands to affect myriad physiological responses. The analysis of toxins acting via hormone receptor mechanisms has recently benefited from many new, more sensitive approaches to this question. Endocrine toxicologists come from a scientific background that fosters expectations that ligands engaging hormone receptors will operate via very diverse and sensitive signaling and metabolic mechanisms. Therefore, we are not at all surprised when endocrine disrupting toxins using this portal to the cellular regulation machinery act very potently and without thresholds.

Newer approaches, especially those utilizing higher throughput in vitro tests, have dramatically increased our ability to analyze low-dose effects of both hormones and the toxins that mimic them, and make detailed structure-activity comparisons. The viewpoint presented by the Dietrich et al. editorial dismisses some of these as “isolated” test systems. However, these new contributions, with their added sensitivity, provide novel insights into diseases caused by the hijacking/blocking of physiological hormone actions, especially during development. These results, along with the results of already-established in vivo and in vitro tests, should all be considered together in our analysis of this question. Those who provided evidence supporting the concept of thresholds, developed many years ago with the best scientific approaches and thinking of those times, should welcome new ways to revisit the question. Claiming that it is settled once-and-for-all because established, widely proven procedures of the past were used to address the question is not good enough. The “stringency of data evaluation that has developed over the past centuries” should not blind us to new approaches and ideas that can be equally stringent in their data evaluation.

Lack of understanding of how new test systems make contributions is one of those cross-disciplinary kinks we will have to work out. The greatest advances in science happen when its practitioners and thinkers from previously separate thought frameworks or “silos” strive to understand each other’s approaches and constructs, so as to gain new insights into long-standing conundrums—in this case, how hormonal regulation is disrupted by low concentrations of contaminants that appear to use endocrine mechanisms. Interactions between disciplines that have long stood separate are painful and messy. New approaches and paradigms should not be rejected just because science and society have invested so much time and money in past assessments, no matter how “accepted and proven” they were. While accumulated understanding is what we use to make decisions at a given point in time, we should not let it become a barrier to gaining new understanding.

The alarming increases in certain chronic diseases that have coincided with greater exposures to modern synthetic chemicals triggered these new ideas and analyses. Therefore, it is not hard to understand the scientific intuition that elicited new examinations of the problem. Fresh ideas and approaches were needed, including examining endocrine-based principles. Reevaluation, and perhaps rewriting of well-accepted previous scientific and regulatory principles and practices, is our only hope for moving forward in understanding, preventing, and remediating these vexing chronic disease escalations for which these new considerations may provide some solutions. We will make far more progress by broadly considering a wide range of biological mechanisms and action levels to allow us to construct a better overall picture of how endocrine-active toxins affect humans and other animals.

We hope that as a new journal, Endocrine Disruptors will help to bridge the current gap between these different interpretations. We invite you to use this platform to focus on the differences between the academic traditions of different fields contributing to endocrine disruption insights, to help resolve the issues. We hope to mine the disagreements constructively to come up with new principles for maintaining public/planetary safety. Presumptions of no harm in effects that we do not fully understand should not make us feel safe.

10.4161/endo.26646

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.