Study Of Endocrine Disrupting Chemicals Research Articles

Study of Endocrine-Disrupting Chemicals in Infant Formulas and Baby Bottles: Data from the European LIFE-MILCH PROJECT.

Exposure to endocrine-disrupting chemicals (EDCs) is inevitable, and growing scientific evidence indicates that even very low doses can negatively impact human health, particularly during pregnancy and the neonatal period. As part of the European project LIFE18 ENV/IT/00460, this study aims to identify the presence of EDCs in 20 infant formulas (both powdered and liquid) and the release from baby bottles and teats. Particularly, sensitization of young people and future parents towards the potential harmful effects of EDCs could significantly help to reduce exposure. Seven different UPLC-MS/MS methodologies and one ICP-AES were set up to quantify already assessed and suspected EDCs among 85 different chemicals (bisphenols, parabens, PAHs, phthalates, pesticides, herbicides and their main metabolites, PFAS, and metals). Results showed that in 2 out of 14 baby bottles, only anthracene and phenanthrene of the group of PAHs were released (10.68-10.81 ng/mL). Phthalates such as mono-ethyl phthalate (MEP) were found in 9 of 14 samples (0.054-0.140 ng/mL), while mono(2-ethyl-5-oxohexyl) phthalate (MeOHP) appeared in 2 samples (0.870-0.930 ng/mL). In accordance with current EU regulations, other chemicals were not detected in baby bottles and teats. However, bisphenols, parabens, PAHs, phthalates, PFAS, and metals were detected in infant formula, emphasizing the need for continued monitoring and public health interventions.

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women.

Recently, there has been a noticeable increase in disorders of the female reproductive system, accompanied by a rise in adverse pregnancy outcomes. This trend is increasingly being linked to environmental pollution, particularly through the lens of Endocrine Disrupting Chemicals (EDCs). These external agents disrupt natural processes of hormones, including synthesis, metabolism, secretion, transport, binding, as well as elimination. These disruptions can significantly impair human reproductive functions. A wealth of animal studies and epidemiological research indicates that exposure to toxic environmental factors can interfere with the endocrine system's normal functioning, resulting in negative reproductive outcomes. However, the mechanisms of these adverse effects are largely unknown. This work reviews the reproductive toxicity of five major environmental EDCs-Bisphenol A (BPA), Phthalates (PAEs), Triclocarban Triclosan and Disinfection Byproducts (DBPs)-to lay a foundational theoretical basis for further toxicological study of EDCs. Additionally, it aims to spark advancements in the prevention and treatment of female reproductive toxicity caused by these chemicals.

General Challenges and Recommendations for the Water Quality Criteria of Endocrine Disrupting Chemicals (EDCs).

Water quality criteria (WQC) play an important role in the environmental management of pollutants in different countries or institutions. It has been found that endocrine disrupting chemicals (EDCs) can potentially alter functions of the endocrine system and consequently cause adverse effects in aquatic organisms. Therefore, the complicated modes of action and mechanisms of EDCs should be carefully considered in WQC studies. For example, the research regarding the WQC derivation of EDCs should prioritize sensitive aquatic species in consideration of the WQC derivation. Second, the chronic toxicity of EDCs should be of utmost concern. In addition, the appropriate effects and endpoints of EDCs should be carefully selected for the WQC derivation. Moreover, it was pointed out that some new methods should be taken into consideration in the WQC studies of EDCs in the near future.

A cross-species comparative approach to assessing multi- and transgenerational effects of endocrine disrupting chemicals

A wide range of chemicals have been identified as endocrine disrupting chemicals (EDCs) in vertebrate species. Most studies of EDCs have focused on exposure of both male and female adults to these chemicals; however, there is clear evidence that EDCs have dramatic effects when mature or developing gametes are exposed, and consequently are associated with in multigenerational and transgenerational effects. Several publications have reviewed such actions of EDCs in subgroups of species, e.g., fish or rodents. In this review, we take a holistic approach synthesizing knowledge of the effects of EDCs across vertebrate species, including fish, anurans, birds, and mammals, and discuss the potential mechanism(s) mediating such multi- and transgenerational effects. We also propose a series of recommendations aimed at moving the field forward in a structured and coherent manner.

Impacts of endocrine-disrupting chemicals on prostate function and cancer.

Because of their historical mode of action, endocrine-disrupting chemicals (EDCs) are associated with sex-steroid receptors, namely the two estrogen receptors (ERα and ERβ) and the androgen receptor (AR). Broadly, EDCs can modulate sex-steroid receptor functions. They can also indirectly impact the androgen and estrogen pathways by influencing steroidogenesis, expression of AR or ERs, and their respective activity as transcription factors. Additionally, many of these chemicals have multiple cellular targets other than sex-steroid receptors, which results in a myriad of potential effects in humans. The current article reviews the association between prostate cancer and the endocrine-disrupting functions of four prominent EDC families: bisphenols, phthalates, phytoestrogens, and mycoestrogens. Results from both in vitro and in vivo models are included and discussed to better assess the molecular mechanisms by which EDCs can modify prostate biology. To overcome the heterogeneity of results published, we established common guidelines to properly study EDCs in the context of endocrine diseases. Firstly, the expression of sex-steroid receptors in the models used must be determined before testing. Then, in parallel to EDCs, pharmacological compounds acting as positive (agonists) and negative controls (antagonists) have to be employed. Finally, EDCs need to be used in a precise range of concentrations to modulate sex-steroid receptors and avoid off-target effects. By adequately integrating molecular endocrinology aspects in EDC studies and identifying their underlying molecular mechanisms, we will truly understand their impact on prostate cancer and distinguish those that favor the progression of the disease from those that slow down tumor development.

Low dose effects challenge the evaluation of endocrine disrupting chemicals

Endocrine disrupting chemicals (EDCs) are found in a range of consumer products including food and food packaging. Both observational and experimental studies suggest that EDCs present in food and consumer products can contribute to diseases. This commentary reviews the current state of knowledge on EDCs including the available infrastructure to evaluate these compounds and limitations to standardized tests used in regulatory toxicology. I then identify the research and technological needs that should be addressed to improve the study of EDCs. Finally, I describe steps that could be taken in the short- and long-term to begin to meet these needs.

Firm human evidence on harms of endocrine-disrupting chemicals was unlikely to be obtainable for methodological reasons

Background and ObjectiveDespite plausible laboratory evidence about harms of endocrine-disrupting chemicals (EDCs), systematic reviews and meta-analyses of epidemiological studies do not consistently find such harms. The purpose of this article was to discuss why solid human evidence on EDCs was unlikely to be obtainable even though they are truely harmful to humans. ResultsIndeed, there are insurmountable methodological limitations in human studies. They include unpredictable net effects of diverse EDC mixtures, low reliability of exposure assessment, nonmonotonic dose-response relationships, nonexistence of an unexposed group, and complicated interactions with diet and obesity. The exposome is never free from these methodological issues. Therefore, the most persuasive evidence about human harms of EDCs may be increasing EDC-linked diseases at population levels, but traditional epidemiological studies of EDCs, especially short-lived and widely used EDCs, fail to provide consistent results. Nevertheless, human studies of EDCs with long half-lives, for example, persistent organic pollutants (POPs), are still worthwhile because there are fewer methodological issues. Also, they can play a role as surrogate markers of lipophilic chemical mixtures. Notably, although POPs are well-known EDCs, human findings on POPs cannot be attributed to common hormone-disrupting properties because the net effect of diverse EDC mixtures cannot be reliably predicted even with POPs. Homeostasis disruption through mitochondrial dysfunction may be more relevant to such effects. ConclusionLogical inference should play a primary role in judging harms of EDCs in humans.

Endocrine disruption through membrane estrogen receptors and novel pathways leading to rapid toxicological and epigenetic effects

Estrogen binding to estrogen receptors (ESR) triggers signaling cascades within cells. Historically, a major emphasis has been characterizing estrogen-induced genomic actions resulting from binding to nuclear estrogen receptor 1 (nESR1). However, recent evidence indicates the first receptors estrogens encounter as they enter a cell, membrane ESR1 (mESR1), also play crucial roles. Membrane and nuclear ESR are derived from the same transcripts but the former are directed to the membrane via palmitoylation. Binding and activation of mESR1 leads to rapid fluctuations in cAMP and Ca+2 and stimulation of protein kinase pathways. Endocrine disrupting chemicals (EDC) that mimic 17β-estradiol can signal through mESR1 and elicit non-genomic effects. Most current EDC studies have focused on genomic actions via nESR1. However, increasing number of studies have begun to examine potential EDC effects mediated through mESR1, and some EDC might have higher potency for signaling through mESR1 than nESR1. The notion that such chemicals might also affect mESR1 signaling via palmitoylation and depalmitoylation pathways has also begun to gain currency. Recent development of transgenic mice that lack either mESR1 or nESR1, while retaining functional ESR1 in the other compartment, will allow more precise in vivo approaches to determine EDC effects through nESR1 and/or mESR1. It is increasingly becoming apparent in this quickly evolving field that EDC directly affect mESR and estrogen signaling, but such chemicals can also affect proportion of ESR reaching the membrane. Future EDC studies should be designed to consider the full range of effects through mESR alone and in combination with nESR.

Promotional Consideration: A Potential Mechanistic Link between Neonicotinoid Insecticides and Hormone-Dependent Breast Cancer.

Promotional Consideration: A Potential Mechanistic Link between Neonicotinoid Insecticides and Hormone-Dependent Breast Cancer.

The developmental basis of disease: Update on environmental exposures and animal models.

At the Prenatal Programming and Toxicity (PPTox) Conference I in 2008, I presented an overview of the developmental origins of health and disease field focusing on environmental chemical exposures and disease outcomes. At that time, I noted that the field was getting off the ground with a focus on developmental exposure to a small number of endocrine disrupting chemicals (EDCs) and disease outcomes across the lifespan in animal models. In this update, I note that the DOHaD field has changed significantly over the last decade. There are new windows of susceptibility including preconception, prepuberty, a focus on the mother and not just the offspring, and a significant focus on the new field of epigenetic transgenerational inheritance. New disease focus areas have sprung up including obesity, type 2 diabetes and fatty liver disease, all with a connection to developmental exposures to EDCs. There is also a focus on the study of new EDCs, molecular mechanisms, the development of new biomarkers of exposure and disease outcomes and studies focusing on intervention and prevention studies.

The Endocrine Society Centennial: No Longer a Surprise: Estrogenic Chemicals in a Multitude of Places.

Nowadays, we are bombarded with information on a large number of endocrine-disrupting chemicals. We hear and read about endocrine-disrupting chemicals on blogs, the web, news stories, television specials, advertisements, and of course scientific articles. Reports claim these ubiquitous compounds are responsible for increased rates of cancer, autism, obesity, hypospadias, and infertility, just to name a few. But it was not always this way. In fact, the scientific study of endocrine-disrupting chemicals is relatively new: a recent PubMed search found a total of 6184 hits for the term, 739 articles in 2015 as compared with 4, 20 years ago in 1995.

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.

BackgroundThe issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs.MethodsWe have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity.ResultsBuilding from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs.ConclusionsWhen using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0156-6) contains supplementary material, which is available to authorized users.

Survey of Intersex Occurrence in Largemouth Bass (Micropterus salmoides) from the Upper Illinois River Waterway

Abstract Intersex condition (ooctyes in testicular tissue) has been documented in many watersheds among a diverse variety of fishes worldwide. However, few studies have tested for the occurrence of the condition in fishes from rivers of the American Midwest. Midwestern watersheds, such as the Illinois River Waterway, U.S.A. may provide important new information about the effects of endocrine disrupting chemicals (EDCs) on fishes because of the variety of urban, industrial, and agricultural land uses within the watersheds. A first step in the study of EDCs in any ecosystem is a survey to document the symptoms of EDC exposure, such as intersex condition. Our objective was to test for intersex condition in male largemouth bass Micropterus salmoides in the lower Des Plaines River, an area directly affected by surface runoff and wastewater effluents from the Chicago Metropolitan Area. Histological analysis indicated that testicular oocytes were present in 21 of 51 (41%) largemouth bass sampled and oocyte numbe...

Methodological issues in human studies of endocrine disrupting chemicals.

Possible harm from endocrine disrupting chemicals (EDCs) in humans is speculated based on two types of evidence; 1) increasing trends of suspected diseases in ecological studies of populations and 2) findings from traditional epidemiological studies of individuals. However, ecological findings are not regarded as direct human evidence of the relation between EDCs and disease, while the evidence among epidemiological studies of individuals is often inconsistent. Thus, a criticism is that linking EDCs and health in human is naively presumed without solid evidence. However, human studies of EDCs are methodologically complex and understanding methodological issues will help to interpret findings from existing human studies and to properly design optimal human studies. The key issues are low reliability of exposure assessment of EDCs with short half-lives, EDC mixtures, possibility of non-monotonic dose-response relationships, non-existence of an unexposed group, difficulties in measuring exposure during critical periods, and interactions with established risk factors. Furthermore, EDC mixtures may affect human health through other mechanisms than traditional endocrine disruption, for example glutathione depletion or mitochondrial dysfunction. Given this complexity, the most plausible scenario in humans is that exposure to EDC mixtures leads to increasing risk of related diseases at the ecological level, but inconsistent associations would be expected in traditional epidemiological studies. Although epidemiologists have long relied on Bradford Hill's criteria to objectively evaluate whether associations observed in epidemiology can be interpreted as causal, there are challenges to use these criteria for EDCs, particularly concerning consistency across studies and the findings of linear dose-response relationships. At the individual level, compared to EDCs with short half-lives, epidemiological studies of EDCs with long half-lives among populations with a relatively low exposure dose range of exposure can likely produce relatively more reliable results, because the measurement of EDCs with long half-lives likely represents typical long-term exposure and populations with exposure in the low range of doses are likely to have a reference group closer to non-exposure.

Plastic bodies in a plastic world: multi-disciplinary approaches to study endocrine disrupting chemicals

In the 1950's and 60's, there was significant development of synthetic materials for use in consumer products. Plastics of all kinds were produced and have since been incorporated into countless materials. Producers of these chemicals and materials have assumed that they would not have effects on humans or wildlife if exposures remained low. Yet evidence from field studies, controlled laboratory animal experiments and epidemiology has challenged this assumption. Many compounds used in plastics have been characterized as endocrine disrupting chemicals (EDCs), chemicals that interfere with the proper functioning of the endocrine system. EDCs present new challenges to both the industries that produce chemicals and manufacture consumer products, as well as the agencies that are tasked to protect public health. This review will address the issue of developmental plasticity – the concept that developing organisms can adapt to various environmental insults to allow the individual to survive. Studies of EDCs have revealed that developing organisms have tremendous capacity to adapt, but not without significant costs to the individual. We will also address recent efforts by environmental health scientists and green chemists to work collaboratively to solve some of the biggest problems in the field of endocrine disruption. We argue that the use of 21st Century tools and sustainability frameworks will help to avoid ‘regrettable replacements’ and provide society with workable solutions to the issue of endocrine disruption. Further, we conclude that a truly sustainable future demands that exposures to EDCs should be eliminated whenever possible.

Regulation of endocrine-disrupting chemicals insufficient to safeguard public health.

The following article, “The Metabolically Healthy but Obese Phenotype Is Associated With Lower Plasma Levels of Persistent Organic Pollutants as Compared With the Metabolically Abnormal Obese Phenotype” (JCEM 2014;99:E1061–E1066) is one of many new studies that links endocrine-disrupting chemicals (EDCs) to disease. The study reports that obese patients with higher blood levels of persistent organic pollutants (POPs) had significantly greater insulin resistance and worse measures of cardiovascular disease compared with obese patients with lower blood levels of POPs. POPs are toxic man-made chemicals used in agricultural, industrial, and manufacturing processes. The study authors suggest that POPs may contribute to the development of insulin resistance and cardiometabolic disease in obese patients. The good news is that POPs have been strictly regulated since the Stockholm Convention in 2004. The bad news is that these chemicals are still omnipresent and are even found in Arctic locations thousands of miles from known sources. Furthermore, there are many other chemicals with endocrine-disrupting effects that are underregulated or not regulated at all. In the United States, federal agencies including the Food and Drug Administration and the Environmental Protection Agency are responsible for identifying and regulating potentially hazardous chemicals. In the European Union (E.U.), the task falls largely to the European Commission, but with the added complexity of implementation at the national level. The Organisation for Economic Cooperation and Development provides a bridge between the U.S. and E.U. systems, establishing protocols that are agreed upon by all participating parties. In all these efforts, however, endocrinologists are woefully underrepresented, if they participate at all, in the processes of assessing and developing policies. As a result, established policies do not take into account critical endocrine principles. Through scientific publications, education, and awareness-raising efforts, the Endocrine Society is working to change this. Many well-designed, heavily reviewed, National Institutes of Health-funded studies show that exposure to even low doses of EDCs can have adverse effects during critical life periods when organisms may be most vulnerable, yet current regulations often disregard these findings. The Endocrine Society asserts that regulatory decisions on the use of EDCs should be made based on the best available science, and the Society has been joined in this call by other major health organizations. Endocrinologists have a valuable and unique insight into the impact of EDCs, and those actively engaged in the development of new knowledge in relevant disciplines should be involved in evaluating the weight of evidence of EDC studies as well as in the design and interpretation of studies that inform the regulation of EDCs. To this end, the Endocrine Society continues to call on policymakers to enhance screening programs for EDCs by incorporating well-defined and accepted principles of endocrinology. Furthermore, the Society urges policymakers to make sure endocrinologists have a seat at the table when determining effective chemical screening and regulatory measures. The Society is increasing knowledge and understanding of EDCs through publication of its 2009 Scientific Statement and 2012 Statement of Principles, EDC programming at ENDO, and ongoing advocacy efforts in the United States and abroad.

Glow Fish: A New Biosensor to Detect How Environmental Estrogens Affect Tissues

Chemicals that mimic natural estrogens have well-documented effects on the reproductive systems of vertebrates, typically acting as endocrine disruptors, but scientists know much less about how these chemicals affect other tissues and body systems. Investigators have explored zebrafish transgenically modified to glow with green fluorescent protein (GFP) as a way to detect effects of different estrogenic chemicals in real time. A British team now confirms and improves upon previous work by developing an even more sensitive transgenic zebrafish biosensor for assessing potential endocrine disruptors [EHP 120(7):990–996; Lee et al.]. Earlier transgenic models reported exposure only in certain tissues or at very high doses. In the current study, the investigators exposed embryonic transgenic zebrafish at 1 hour postfertilization to environmentally relevant doses of five different estrogenic chemicals: the plasticizer bisphenol A (BPA), the industrial surfactant 4-nonyl-phenol (NP), the natural steroids estrogen and 17β-estradiol (E2), and 17α-ethinylestradiol (EE2), a synthetic hormone widely used in contraceptive pills and hormone replacement therapy. A new transgenic zebrafish model offers a more sensitive method for studying responses to environmentally relevant doses of estrogenic chemicals. These images show 4-day-old zebrafish larvae exposed as embryos to water alone (top) or to water ... Tissues such as the liver, forebrain, lateral line (a sensory system found in aquatic vertebrates), otic vesicles, eyes, heart, and cranial and somite muscle appeared to be strongly affected by some of the compounds tested, but not others. The study also found that different tissues’ response to EE2 was time dependent. For example, liver, heart, and muscle tissue began to glow 24 hours postfertilization and reached maximum strength at 96 hours, whereas a significant increase in fluorescence was seen in the otic vesicles 48 hours postfertilization, and in the eyes and forebrain after 72 hours. Based on this study, the zebrafish biosensor seems a promising and powerful system to test the impacts of a variety of estrogenic chemicals in a living vertebrate at low, environmentally relevant doses. The authors suggest the system could be developed for high-throughput screening, an urgent need in the study of endocrine-disrupting chemicals.

Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses.

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. We review 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.

ENDOCRINE DISRUPTION: Developmental Picture Window

The concept of endocrine disruption emerged in the early 1990s with the observation that natural and industrial compounds were interfering with sex hormone signaling, thereby adversely affecting male and female reproductive health. Since then, many endocrine-disrupting chemicals (EDCs) have been identified, and the field now comprises thousands of studies encompassing virtually every system in the body. On 10 February 2009, the Paonia, Colorado–based nonprofit group The Endocrine Disruption Exchange (TEDX) unveiled the Critical Windows of Development timeline (http://www.criticalwindows.com). The timeline provides a snapshot of the state of the science of when organs and systems develop, when they are vulnerable to particular EDC exposures, and what effects have been observed. Endocrine disruption is not confined to the reproductive system because virtually every system in the body is hormonally responsive. The effects can differ depending on when exposure occurred. For example, according to the timeline, prenatal exposure in mice to bisphenol A (BPA) at gestational days 11.5–18.5 is associated with abnormal fetal egg cell development whereas exposure at gestational days 15–18 is associated with structural changes to the vagina. Theo Colborn, president of TEDX, first conceptualized condensing the body of EDC literature into a user-friendly graphic format. Despite Colborn’s optimism concerning the timeline’s feasibility, it took several years to figure out how to present the data visually. “We had the data here, and we had everything in boxes, but displaying it in the picture we wanted to create was complex,” says Colborn. An early attempt involved an extraordinary expanse of butcher paper; a collaboration with Carol Kwiatkowski, now executive director of TEDX, helped bring Colborn’s vision to fruition. “As far as we know, there’s nothing out there like it,” says Kwiatkowski, who organized and then funneled the research into a database before finding the web developer who could translate it into the desired visual display. The display comprises a series of horizontal bars, each depicting a specific system or organ for the full 38 weeks of human pregnancy. Corresponding time points in rodent development are indicated along the top of the screen. Tick marks along the bars indicate studies done at specific time points corresponding to points in normal human development. Another series of tick marks indicates EDC studies performed in the laboratory. Clicking on a mark brings up a concise summary of the study details with a link to the PubMed record. All chemical studies notated on the timeline must be original research using rodent or human cells or tissues. Exposures of parts per million or less to an EDC must have occurred during a time point equivalent to some point in human pre-natal development. “We wanted to keep it within a range [representing the point] where we know from the literature on ambient exposures and monitoring studies that humans might be exposed,” says Colborn. The timeline is currently populated with all existing BPA studies that meet the criteria for inclusion; staff are still plotting dioxin and phthalate studies. New studies will be inserted upon publication, and more chemicals will be incorporated into the timeline in the coming year. The timeline, which is free to all users, fills several needs at once. “One of the needs that has become apparent over the years has been just a basic reference for normal development in both humans and rodent models,” says Kris Thayer, a health science administrator at the NIEHS. To begin to grasp how various systems are affected by endocrine disruption, it is necessary to know when those systems are developing. “What Theo has done is to develop a graphic tool—it’s very visual, very interactive, and very well referenced—so you can easily see everything in one place,” says Thayer. Jerry Heindel, a scientific program administrator at the NIEHS, says the time-line could be useful in determining areas where research is needed and how to plan new studies. “Even a cursory examination of the tick marks that show when experiments have been done provides a nice overview of the timing of studies throughout development,” he says. “This information can then be used to refine the timing, doses, and end points of future studies.” Colborn also hopes the timeline will inspire scientists to take a broader view of endocrine disruption and possibly promote collaboration across systems. Researchers tend to focus on one system or organ at a time, she says, and as a result a lot of information that could be gleaned from carefully controlled experiments is never gathered. “I think the timeline will be very useful for researchers [from many disciplines], especially as people cut across different biological systems,” says Thayer. “The information on the timeline is contained in reference books and research journals, but it’s very handy to have it all in one place.”

Bisphenol A Effects on the Growing Mouse Oocyte Are Influenced by Diet1

Growing evidence suggests that exposure to bisphenol A (BPA) has the ability to disrupt several different stages of oocyte development. To date, most attention has focused on the effects of BPA on the periovulatory oocyte, and considerable variation is evident in the results of these studies. In our own laboratory, variation in the results of BPA studies conducted at different times appeared to correlate with changes in mill dates of animal feed. This observation, coupled with reports by others that dietary estrogens in feed are a confounding variable in studies of endocrine-disrupting chemicals, prompted us to evaluate the effect of diet on the results of BPA studies of the periovulatory oocyte. Genetically identical females were placed on a high- or low-phytoestrogen diet prior to mating. Their female offspring were exposed to BPA, oocytes collected, and meiotic spindle and chromosome characteristics compared between control and BPA-treated females. We observed significant diet-related variation in both the frequency of abnormalities in oocytes from untreated females and in the response to BPA. Our results demonstrate that the impact of BPA on meiosis depends, at least in part, on diet. We suggest that variation in the conclusions of recent BPA studies reflects differences in the diets used, as well as other methodological differences. Because meiotic disturbances are a feature of all studies to date, however, we conclude that low levels of BPA adversely affect the meiotic process.