Paonia, CO, United States
Paonia, CO, United States

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Vandenberg L.N.,Tufts University | Colborn T.,The Endocrine Disruption Exchange | Hayes T.B.,University of California at Berkeley | Heindel J.J.,U.S. National Institutes of Health | And 8 more authors.
Endocrine Reviews | Year: 2012

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. Wereview the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. © 2012 by The Endocrine Society.


PubMed | University of California at Irvine, Consumers Union, The Endocrine Disruption Exchange, L. Everett & Associates and 7 more.
Type: | Journal: Environmental health : a global access science source | Year: 2016

The broad-spectrum herbicide glyphosate (common trade name Roundup) was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organizations International Agency for Research on Cancer recently concluded that glyphosate is probably carcinogenic to humans. In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention.


Schug T.T.,U.S. National Institutes of Health | Johnson A.F.,MDB Inc | Birnbaum L.S.,U.S. National Cancer Institute | Colborn T.,The Endocrine Disruption Exchange | And 8 more authors.
Molecular Endocrinology | Year: 2016

Within the past few decades, the concept of endocrine-disrupting chemicals (EDCs) has risen from a position of total obscurity to become a focus of dialogue, debate, and concern among scientists, physicians, regulators, and the public. The emergence and development of this field of study has not always followed a smooth path, and researchers continue to wrestle with questions about the low-dose effects and nonmonotonic dose responses seen with EDCs, their biological mechanisms of action, the true pervasiveness of these chemicals in our environment and in our bodies, and the extent of their effects on human and wildlife health. This review chronicles the development of the unique, multidisciplinary field of endocrine disruption, highlighting what we have learned about the threat of EDCs and lessons that could be relevant to other fields. It also offers perspectives on the future of the field and opportunities to better protect human health. © 2016 by the Endocrine Society.


Colborn T.,The Endocrine Disruption Exchange | Schultz K.,The Endocrine Disruption Exchange | Herrick L.,The Endocrine Disruption Exchange | Kwiatkowski C.,The Endocrine Disruption Exchange
Human and Ecological Risk Assessment | Year: 2014

This exploratory study was designed to assess air quality in a rural western Colorado area where residences and gas wells co-exist. Sampling was conducted before, during, and after drilling and hydraulic fracturing of a new natural gas well pad. Weekly air sampling for 1 year revealed that the number of non-methane hydrocarbons (NMHCs) and their concentrations were highest during the initial drilling phase and did not increase during hydraulic fracturing in this closed-loop system. Methylene chloride, a toxic solvent not reported in products used in drilling or hydraulic fracturing, was detected 73% of the time; several times in high concentrations. A literature search of the health effects of the NMHCs revealed that many had multiple health effects, including 30 that affect the endocrine system, which is susceptible to chemical impacts at very low concentrations, far less than government safety standards. Selected polycyclic aromatic hydrocarbons (PAHs) were at concentrations greater than those at which prenatally exposed children in urban studies had lower developmental and IQ scores. The human and environmental health impacts of the NMHCs, which are ozone precursors, should be examined further given that the natural gas industry is now operating in close proximity to human residences and public lands. © 2014 Copyright Taylor and Francis Group, LLC.

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