Disruption In Wildlife Research Articles

Planar chromatography-bioassays for the parallel and sensitive detection of androgenicity, anti-androgenicity and cytotoxicity

Anti-androgens entering the aquatic environment, e.g., by effluents from wastewater treatment plants or agricultural settings are contributing to endocrine disruption in wildlife and humans. Due to the simultaneous presence of agonistic compounds, common in vitro bioassays can underestimate the risk posed by androgen antagonists. On the other hand, cytotoxic effects might lead to false positive assessments of anti-androgenic effects in conventional bioassays. In the present study, a combination of normal phase high-performance thin-layer chromatography (NP-HPTLC) with a yeast-based reporter gene assay is established for the detection of anti-androgenicity as a promising tool to reduce interferences of androgenic and anti-androgenic compounds present in the same sample. To avoid a misinterpretation of anti-androgenicity with cytotoxic effects, cell viability was assessed in parallel on the same plate using a resazurin viability assay adapted to HPTLC plates. The method was characterized by establishing dose-response curves for the model compounds flutamide and bisphenol A. Calculated effective doses at 10% (ED10) were 27.9 ± 1.3 ng zone−1 for flutamide and 20.1 ± 5.1 ng zone−1 for bisphenol A. Successful distinction between anti-androgenicity and cytotoxicity was exemplarily demonstrated with 4-nitroquinoline 1-oxide. As a proof of concept, the detection and quantification of anti-androgenicity in an extract of a landfill leachate is demonstrated. This study shows that the hyphenation of HPTLC with the yeast anti-androgen screen is a matrix-robust, cost-efficient and fast screening tool for the sensitive and simultaneous detection of anti-androgenic and cytotoxic effects in environmental samples. The method offers a wide range of possible applications in environmental monitoring and contributes to the identification of anti-androgenicity drivers in the course of an effect-directed analysis.

Environmental toxic Endocrine Disrupting Compounds (EDCs): Effects on environment, animal production and human

Endocrine disrupting compounds (EDCs) encompass a variety of chemical classes, including several different categories of substances. Some are natural, such as plant oestrogens and mycoestrogens, while most are chemically composed. Residues are found in water, in sewage sludge, in the atmosphere and in foodstuff of vegitative or animal origin. The most common compounds include organochlorine pesticides, alkyl phenols, pthalates, polychlorinated biphenyls (PCBs), dioxins and polybrominated diphenyl ethers (PBDEs). Their properties render some as ubiquitous and persistent in the environment, they can be transported long distances and have been found in virtually all regions of the world. Their sources can vary from direct, such as effluents from wastewater, sewage, industrial sludge processes or agricultural effluents, to indirect, such as filtering agricultural soils, transportation through rain or air from civil and industrial centers to rivers and the surrounding environment. Others are rapidly degraded in the environment or human body or may be present for only short periods of time, but at critical periods of development. Although in low concentrations, the continuous exposure of animals of many species, including humans, induces adverse effects, such as disruption of reproductive function and of the immune system, as well as carcinogenic effects. The effects are obvious in wildlife, especially fish, and laboratory experiments. Sex change (feminizing) in fish has been observed, sexual differentiation in rats, egg shelling thinning, thyroid function disruption and mental and physical function disruption in wildlife. Most important and common is the disruption in the reproductive and the immune system of animals. As far as humans are concerned, reduction in sperm count and sperm quality has been heavily linked with EDC exposure, and furthermore, suspicions arise linking several cancer incident increments, such as testicular cancer, to EDC exposure. Still, although it is clear that many environmental chemicals can interfere with normal hormonal processes, there is weak evidence that human health can be adversely and directly affected by exposure to endocrine active chemicals. However, there is sufficient evidence to conclude that adverse endocrine mediated effects have occurred in wildlife species and laboratory studies exist to support these conclusions. The routes of exposure are numerous. Food is a common route of exposure, especially in younger animals that consume food containing higher fat percentages (e.g. milk). Soil is another route of exposure. Thus grazing animals tend to have a higher risk factor, due to surface soil pollution with EDCs. A vegetative nutrition with EDC residues is another high risk factor for these animals. On the other hand, animals bred with forage tend to be at lower risk factor, given that food is tested for low levels of EDCs. Water intake is not considered a significant route of exposure. EDCs possess the ability to act as either hormone agonists or antagonists or disrupt hormone synthesis, storage or metabolism. Due to their persistence in the environment, they are concentrated in fat tissue and are released when the fat is mobilized duringpregnancy or lactation, thus exposing embryos and neonates, which are very susceptible at this stage of development, to high concentrations of EDCs. The concerns that arise regarding the exposure to these EDCs are due primarily to:- these adverse effects observed in certain wildlife, fish and ecosystems- the increased incidences of certain endocrine-related human diseases and- endocrine disruption resulting from exposure to certain environmental chemicals observed in laboratory experimental animals.

Distribution and Removal of Nonylphenol Ethoxylates and Nonylphenol from Textile Wastewater—A Comparison of a Cotton and a Synthetic Fiber Factory in Vietnam

The textile industry is a significant source of nonyphenol and their ethoxylates, which are suggested to be responsible for endocrine disruption in wildlife and humans. This study is a comparison of two conventional wastewater treatment processes in a cotton and a synthetic fiber factory in Vietnam, with regard to the distribution and removal of nonyphenol ethoxylates and nonyphenol throughout each process. Diverse trends in the distribution of nonyphenol ethoxylates in wastewater from factories, distinguished by their raw materials, could be revealed. Primary coagulation might not perfectly facilitate nitrification in the secondary activated sludge process regarding pH. Nevertheless, satisfactory removals were achieved during coagulation and activated sludge processes in both systems. The roles of long hydraulic retention times (21 and 16 h, respectively), low organic loadings (0.1 and 0.2 gCOD/gMLVSS.day, respectively), extended solids retention times (61 and 66 days, respectively), and mixed liquor suspended solids of greater than 2000 mg/L have been demonstrated. The findings provide evidence and a better understanding of nonyphenol ethoxylate and nonyphenol removal efficacy as well as influencing factors in Vietnamese textile wastewater treatment. The results are beneficial for the textile industry in Vietnam regarding investment decisions for wastewater treatment.

17α-ethynilestradiol and tributyltin mixtures modulates the expression of NER and p53 DNA repair pathways in male zebrafish gonads and disrupt offspring embryonic development

Although chemicals are usually present in the environment in complex mixtures, ecotoxicological risk assessments often rely on data from single exposures to contaminants. The present study aimed at examining the effects of two ubiquitous endocrine disrupting chemicals (EDCs), 17α-ethynilestradiol (EE2) and tributyltin (TBT), single and combined, in zebrafish (Danio rerio) reproduction and embryonic development, and to investigate the impact on DNA repair molecular pathways.Chronic life-cycle exposure to environmental relevant concentrations of both EDCs led to significant effects on reproduction and embryonic development. TBT exposure at 50 ng/L impacted the percentage of fertilized eggs. EE2 exposure at 0.75 and 1.75 ng/L and the mixture treatments (0.75 and 1.75 ng/L EE2 plus 50 ng/L TBT) led to a sex bias towards females. Furthermore, EE2 exposure at 1.75 ng/L and the mixture of EE2 (1.75 ng/L) and TBT (50 ng/L) impaired embryonic development. The study of DNA repair pathways indicated that EE2 and TBT, single and combined, significantly modulated the expression levels of key DNA repair genes in male gonads, such as xpc nucleotide excision repair (NER) pathway gene as well as the tumor suppressor p53, its target effectors, i.e. p21, gadd45α and bax, and p53 key regulator (mdm2). The observed impact in the transcription of these genes supports the hypothesis of an effect of EE2, TBT, and their combined mixtures, on DNA repair pathways, thus suggesting that impairment of embryonic development of F2 generation could be linked to the disruption of DNA repair processes in the gonads of individuals from the parental generation. Taken together, these findings contribute to a better understanding of the impact of mixtures of the ubiquitous contaminants EE2 and TBT, strongly supporting the inclusion of embryonic development and gene expression studies in the screening of endocrine disruption in wildlife.

Retraction Note to: Fate and Transport of EDCs in Soils: Estrone and its Sulfate Conjugate's Adsorption from Mediator Solutions

The fate and transport of emerging contaminants have been major concerns for ecoenvironment and human health. This study presents the adsorption behavior of an endocrine disrupting chemical estrone (E1) and its sulfate conjugate estrone-3-sulfate (E1-3S) that are released to the environment via animal waste in significant amounts and direct exposures in grazed pasture systems. Both compounds have been shown to potentially contribute to endocrine disruption in wildlife, and knowledge about the adsorption behavior of these compounds is necessary for a sound environmental risk assessment. For labile compounds such as E1 and E1-3S, however, the standard protocols might overestimate adsorption by not considering metabolite formation or allowing for equilibration that exceeds the commonly reported half-lives of these compounds. Modified batch adsorption experiments with mediator solution of 0.005 M calcium chloride (CaCl2) and artificial urine (AU) solution were, therefore, conducted to determine the influence of these mediator solutions on the adsorption of E1 and E1-3S in three agricultural soils from Nasarawa State of Nigeria. Adsorption isotherms of both compounds were nonlinear, and the Freundlich equation was found adequate to describe the isotherms. The calculation of concentration-dependent effective distribution coefficients (K d eff) revealed that for a range of realistic exposure concentrations in a grazed farming system, the common approach of using CaCl2 would deliver incorrect information for a sound risk assessment.

Well Water in Karst Regions of Northeastern Wisconsin Contains Estrogenic Factors, Nitrate, and Bacteria

Well water in karst regions is particularly susceptible to contamination by various nonpoint source pollutants such as nitrate, fecal bacteria, and endocrine disrupting chemicals (EDCs). This study analyzed 40 wells in heavily farmed karst areas of northeastern Wisconsin to determine whether these and other pollutants are present, and if so, whether their presence is (1) correlated with other contaminants and (2) exhibits seasonal variation. Nitrate, bacteria, and estrogenicity (indicating the presence of EDCs) were present in at least some of well water samples collected over the course of four time periods between the summers of 2008 and 2009. Although estrogenicity was greatest during the summer months, bacterial contamination was most prevalent during snowmelt. Levels of estrogenicity present in some well water samples approached a threshold concentration that is known to exert endocrine disruption in wildlife. Strong correlations between estrogenicity and other water quality parameters were not found.

The Effects of Wastewater Effluent on Sexual Differentiation and Gene Expression in the American Bullfrog

The Effects of Wastewater Effluent on Sexual Differentiation and Gene Expression in the American Bullfrog

Differences in sensitivity but not selectivity of xenoestrogen binding to alligator versus human estrogen receptor alpha

Reproductive abnormalities in alligators exposed to contaminants in Lake Apopka, Florida, USA represent a clear example of endocrine disruption in wildlife. Several of these contaminants that are not able to bind to mammalian estrogen receptors (such as atrazine and cyanazine) have previously been reported to bind to the alligator estrogen receptor from oviductal tissue. Binding of known Lake Apopka contaminants to full length estrogen receptors alpha from human (hERalpha) and alligator (aERalpha) was assessed in a side-by-side comparison within the same assay system. Baculovirus-expressed recombinant hERalpha and aERalpha were used in a competitive binding assay. Atrazine and cyanazine were not able to bind to either receptor. p,p'-Dicofol was able to bind to aERalpha with a concentration inhibiting 50% of binding (IC50) of 4 microM, while only partially displacing 17beta-estradiol (E2) from hERalpha and yielding a projected IC50 of 45 microM. Chemicals that only partially displaced E2 from either receptor, including some dichlorodiphenyltrichloroethane (DDT) metabolites and trans-nonachlor, appeared to have higher affinity for aERalpha than hERalpha. p,p'-Dicofol-mediated transcriptional activation through aERalpha and hERalpha was assessed to further explore the preferential binding of p,p'-dicofol to aERalpha over hERalpha. p,p'-Dicofol was able to stimulate transcriptional activation in a similar manner with both receptors. However, the in vitro results obtained with p,p'-dicofol were not reflected in an in vivo mammalian model, where Kelthane (mixed o,p'- and p,p'-dicofol isomers) did not elicit estrogenic effects. In conclusion, although there was no evidence of exclusively species-specific estrogen receptor binders, some xenoestrogens, especially p,p'-dicofol, had a higher affinity for aERalpha than for hERalpha.

Sorption of estrone and estrone‐3‐sulfate from CaCl2 solution and artificial urine in pastoral soils of New Zealand

Estrone (E1) and its sulfate conjugate estrone-3-sulfate (E1-3S) are released to the environment in animal wastes in significant amounts, and direct exposure occurs in grazed pasture systems. Both compounds have been shown to potentially contribute to endocrine disruption in wildlife, and knowledge about the sorption behavior of these compounds is necessary for a sound risk assessment. For labile compounds such as E1 and E1-3S, however, the standard protocols might overestimate sorption by not considering metabolite formation or allowing for equilibration that exceeds the commonly reported half-lives of these compounds. We therefore conducted modified batch sorption experiments with 0.005 M calcium chloride (CaCl2) and artificial urine solution to determine the influence of the mediator solution on the sorption of E1 and E1-3S in three pasture soils from New Zealand. Sorption isotherms of both compounds were nonlinear, and the Freundlich equation was found adequate to describe the isotherms. The sorption potential of E1-3S was about one order of magnitude lower than for the free counterpart, and the Kf values significantly changed between the two mediator solutions. The calculation of concentration-dependent effective distribution coefficients (Kdeff) revealed that for a range of realistic exposure concentrations in a grazed dairy system, the common approach of using CaCl2 would deliver incorrect inferences for a sound risk assessment.

Methodology for Profiling the Steroid Metabolome in Animal Tissues Using Ultraperformance Liquid Chromatography−Electrospray-Time-of-Flight Mass Spectrometry

The advent of mass spectrometry-based metabolite profiling techniques should allow investigations into the behavior and regulation of many of the low abundant signaling molecules present in the animal metabolome such as hormones and so aid investigations into the mechanisms of endocrine system function and disorders. Examples of their potential applications include endocrine-related diseases such as some cancers, as well as endocrine disruption in wildlife and humans caused by some environmental contaminants. In the present study, a method was developed to profile a variety of vertebrate steroids and their conjugates in fish tissues using solid phase extraction (SPE) prior to ultraperformance liquid chromatography linked to electrospray-time-of-flight mass spectrometry (UPLC-TOF MS). Analysis of tissue extracts spiked with steroids revealed that most analytes could be detected at subnanogram per gram concentrations in liver or testes, but ovarian extracts caused ion suppression of estrogens. A comparison of the steroid metabolome of the ovaries and testes using partial least-squares discrimination analysis (PLS-DA) revealed that the androgens 11-ketotestosterone, 11-hydroxyandrostenedione, androstenedione, and two unidentified cortisol-type glucocorticoids were discriminatory steroid markers in testes extracts. In contrast, cortisol was the predominant glucocorticoid marker in ovary extracts, and cortisone was abundant in extracts of both testes and ovaries. A number of other unidentified nonsteroidal metabolites were also differentially expressed between the testes and ovarian tissues. These studies reveal that metabolite profiling using UPLC-TOF MS is a promising approach to investigate steroid homeostasis in animal tissues.

Plasma vitellogenin in Morelet's crocodiles from contaminated habitats in northern Belize

Vitellogenin induction has been widely used as a biomarker of endocrine disruption in wildlife, but few studies have investigated its use in wild reptiles living in contaminated habitats. This study examined vitellogenin induction in Morelet's crocodiles ( Crocodylus moreletii) from wetlands in northern Belize contaminated with organochlorine (OC) pesticides. Vitellogenin was measured in 381 crocodile plasma samples using a vitellogenin ELISA previously developed for this species. Vitellogenin was detected in nine samples, all from adult females sampled during the breeding season. Males and juvenile females did not contain detectable levels of vitellogenin; however, many of these animals contained OC pesticides in their caudal scutes, confirming contaminant exposure. The lack of a vitellogenic response in these animals may be attributable to several factors related to the timing and magnitude of exposure to endocrine-disrupting chemicals and should not be interpreted as an absence of other contaminant-induced biological responses.

Imposex induction is mediated through the Retinoid X Receptor signalling pathway in the neogastropod Nucella lapillus

The imposex phenomenon in female prosobranch gastropods provides one of the best documented examples of endocrine disruption in wildlife. While many field studies have demonstrated the negative impact of tributyltin (TBT) upon female gastropods, the mechanism(s) underlying imposex development has not yet been fully clarified. Over the years several hypotheses have been raised to determine the biochemical and molecular determinants of this process. Nevertheless, the interplay between the different suggested pathways (neuroendocrine, steroid and retinoid) is still unknown. Hence, through a combination of exposure experiments, we show that the 9- cis-retinoic acid (9cisRA), the proposed natural ligand of the retinoic X receptor (RXR), induces imposex in females of Nucella lapillus to the same degree as tributyltin, when administered at similar concentrations (1 μg/g body weight). Methoprene acid, a selective ligand for RXR, also induces imposex, albeit to a lower degree than that of the positive control. In contrast, testosterone significantly induced imposex, but had no effect on female penis induction, while the neuropeptide APGWamide had no effect on imposex development. These results clearly demonstrate that imposex induction in N. lapillus is mediated through the modulation of the RXR signalling pathways. In addition to the effects reported in female dogwhelks, both TBT and RA significantly increased male penis length, thus suggesting that TBT may also impact male secondary sex organs through the RXR signalling pathways. As a step for future studies, we have cloned the orthologue of N. lapillus RXR and provide experimental evidence that it binds 9cisRA. Finally, the basal expression level of RXR in several tissues of N. lapillus was determined through real-time PCR, thus showing that RXR is ubiquitously expressed in mollusc tissues, with the highest expression levels being recorded in female and male gonads. The mechanistic impacts of the overall findings to the imposex process are discussed.

Introduction: Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects

With the aim of discussing new research findings about chemicals able to interfere with the endocrine system, so-called endocrine disruptors, an international workshop was held in Prague, Czech Republic, 10–12 May 2005. The workshop was organized jointly by the EDEN project (Endocrine Disrupters: Exploring Novel Endpoints, Exposure, Low-Dose and Mixture-Effects in Humans, Aquatic Wildlife and Laboratory Animals; http://www.edenresearch.info) and the FIRE project (Risk Assessment of Brominated Flame Retardants as Suspected Endocrine Disrupters for Human and Wildlife Health; http://www.rivm.nl/fire), both large-scale consortia funded by the European Union (EU). The meeting was attended by more than 170 scientists from academia, industry, government agencies, and other organizations. EDEN and FIRE were part of the CREDO cluster (Cluster for Research on Endocrine Disruption), an umbrella organization of more than 60 EU-funded laboratories working on endocrine disruptors. Together with the COMPRENDO (Comparative Research on Endocrine Disruption) and the EURISKED projects (Multi-organic Risk Assessment of Selected Endocrine Disruptors; http://www.eurisked.org), EDEN and FIRE formed the core of the cluster. CREDO served as a platform for cooperation and exchange between its constituent projects. With the completion of almost all its member projects, CREDO has recently ceased to exist, but information about the cluster is still available on online (http://www.credocluster.info). The Prague workshop was the last in a series of meetings organized under the auspices of the CREDO cluster. The themes of previous workshops were risk assessment and the ecologic relevance of chemically induced endocrine disruption in wildlife (Jobling and Tyler 2006). This monograph contains papers presented at the Prague workshop and follows the session structure of the meeting, focusing on four main topics: “Indicators of Human and Wildlife Exposure to EDCs ” reports on new findings relating human exposure to endocrine disruptors in Europe to reproductive disorders, including cryptorchidism, hypospadias, and semen quality. New information about exposure trends for brominated flame retardants in freshwater and marine ecosystems is also given. “Novel models, end points, and biomarkers” summarizes research on the effects of endocrine disruptors on steroid-metabolizing enzymes and gives new data on alkylphenols as endocrine disruptors. Additional articles focus on the consequences of prolonged phytoestrogen exposure for reproductive organs and the outcomes of in utero exposure to endocrine disruptors for testicular dysgenesis, prostate development, and the thyroid hormone axis. “Low-dose effects of endocrine disruptors” gives a synthesis of recent observations in in vitro systems and highlights the importance of statistical power considerations in resolving the low-dose issue. “Mixture effects of endocrine disruptors and their assessment” contains reviews of combination effects, assesses the implications of low-level exposure to multiple chemicals and describes the joint effect of endocrine disruptors in fish and in a developmental toxicity rat model. Taken together, the articles presented in this monograph capture a great deal of the lively debates that took place during the Prague workshop and within the CREDO cluster as a whole. The workshop made considerable progress toward answering key questions that were unresolved a few years ago. It has also stimulated a consensus statement among scientists actively engaged in research in this field, the “Prague Declaration on Endocrine Disruption.” The Prague Declaration, also published as part of this monograph (available as Supplemental Material online at http://www.ehponline.org/docs/2007/10517/suppl.pdf), summarizes issues upon which the majority of scientists can agree, outlines research priorities for the next decade, and highlights steps that can be taken today to prevent health risks to humans and wildlife. It has been signed by more than 200 scientists from all over the world. All contributors to the workshop are thanked cordially. Without their enthusiasm and hard work the meeting and this monograph would not have happened.

Chemical Mixtures: Hayes Responds

LeBlanc and Wang point out that we did not demonstrate synergy; they stated that “to invoke synergy, one must—at a minimum—exclude the possibility of concentration or response additivity.” In fact, we did not “invoke synergy”: in our article, not once did we use the word “synergy.” LeBlanc and Wang themselves “invoke synergy” simply to show that it cannot be invoked from the current study; their problem is with what they inferred from our article, not with any claims that we made. LeBlanc and Wang also point out that our “experiments were not designed to assess concentration additivity, so no judgment can be made either in favor of or against the possibility that the toxicity of the mixture represented concentration additivity.” We agree. This was not the aim of the study. In fact, LeBlanc and Wang’s thesis here is merely a restatement of our own conclusions: The present effects of mixtures cannot be assigned to the categories of concentration additive or response additive. (Hayes et al. 2006; p. 47) and The examinations needed to characterize pesticide interactions as concentration additive or response additive … are difficult to design and carry out and present new challenges to regulators. Such studies are necessary, however (Hayes et al. 2006; p. 48) Finally, LeBlanc and Wang examined our data for response additivity using a simple model and testing select parameters that fit their model while ignoring others. In our study we examined effects of nine pesticides alone (0.1 ppb) or in three different mixtures at 0.1 ppb and 10 ppb on leopard frog (Rana pipiens) larvae. Each treatment (30 larvae/tank) was replicated three times (1,350 larvae total). We assessed effects on 10 parameters: time to foreleg emergence (FLE) and time to complete tail resorption (TR), snout-vent length (SVL) and body weight (BW) at metamorphosis, mortality, gonadal development, thymus histology, disease rates, and the interaction between time to TR and SVL and BW at metamorphosis. Yet, according to LeBlanc and Wang, we simply assessed the effects of nine pesticides individually (at 0.10 ppb) and in combination (each at 0.10 ppb) on time to foreleg emergence and time to complete tail resorption. LeBlanc and Wang used their simple model to show that the effects of one of the pesticide mixtures on developmental time are predictable from the nonsignificant effects of the individual pesticides. Although they predicted the effects of a single pesticide mixture on a single variable, can their model predict the effects of even the single pesticides (propiconazole, λ-cyhalothrin, and atrazine) on the interaction between development and growth (Figure 5; Hayes et al. 2006), when none of these compounds significantly affected development alone and only atrazine affected size alone? Can their model predict the effects of atrazine plus S-metolachlor on the relationship between development and size or explain why the “inert” ingredients in the commercial mixture (Bicep II magnum; Syngenta Crop Protection U.S., Research Triangle Park, NC) appear to reduce this effect? Most certainly, the 70% meningitis infection rate in the surviving animals exposed to the nine-compound mixture cannot be predicted from exposure to the single pesticides, where disease rates were zero. The effect on development was the only parameter that fit LeBlanc and Wang’s model and thus explains their reason for focusing on this single measure and ignoring the other nine parameters we measured. In conclusion, the questions raised in our article (Hayes et al. 2006) can be answered only with empirical evidence obtained from appropriately designed and carefully conducted laboratory experiments, not by simplified models that ignore interactions between independent variables and relationships between dependent variables. Finally, and most important, our data clearly show that examining individual pesticides one at a time does not reveal the magnitude of effects of low-dose chronic exposure to pesticide mixtures and thus does not allow us to accurately assess their impacts on amphibians. Practically all of the chemicals we examined had no significant effects alone, but this was certainly not the case when they were combined. Whether or not these interactions are response additive, concentration additive, or synergistic is irrelevant to the real question: Are we underestimating the impact? If we continue to base assessments on examinations of single compounds, the answer is “yes.”

Introduction: The Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife

Over the last two decades, there has been increasing scientific concern and public debate regarding the adverse effects of chemical pollutants in the environment that can interfere with the normal functioning of the endocrine system in wildlife and in humans (the so-called endocrine-disrupting chemicals, EDCs). These concerns have been fueled primarily by reports of disrupted reproductive function and development in certain wildlife—mammals, birds, fish, amphibians, and mollusks—and by the increased incidence of certain diseases of the endocrine system in humans. Investigators hypothesize that EDCs are the cause. Some of the adverse effects observed in wildlife species are strongly associated with exposure to chemicals that mimic or interfere with hormone function, particularly estrogen function, but in many cases, the causal link between exposure to EDCs and endocrine disruption is unclear. Because of the diverse effects of EDCs on the thyroid, retinoid, androgen, estrogen, and corticosteroid systems of a wide range of animals, it is imperative that research continues to address the extent of the risk posed by EDCs to wildlife. The ecological relevance of endocrine disruption in wildlife is, however, difficult to quantify, as there is limited understanding of how physiological changes affect the individual animal and how individual responses affect population and community. Furthermore, a major challenge faced by environmental biologists is the need to place endocrine disruption into context with other environmental pressures faced by our wildlife populations, for example, global warming.

Policy: New Environment Law for Afghanistan

In April 2005, Afghan president Hamid Karzai established the National Environmental Protection Agency (NEPA), the country’s first such entity. The event was strictly ceremonial, since Afghanistan still had no legal tool for environmental management. Eight months later, however, on 18 December 2005, the Afghan cabinet approved legislation that for the first time gives Afghanistan the legal power it needs to begin bettering its environment. Known as the Environment Act, the law clarifies administrative roles at the national level and coordination with provincial authorities. It spells out frameworks for managing natural resource conservation and biodiversity, drinking water, pollution control, and environmental education. Equally as important, say its supporters, the law provides tools for enforcement. “It seems to be a pretty sensible act,” says David Hanrahan, lead environmental specialist for South Asia at the World Bank. For example, the law’s environmental impact assessment process was guided by a review of 10 countries’ experience and vetted by environmental law experts at the World Bank, the World Conservation Union, and the UN, as well as by Afghan groups. NEPA proposed the legislation based on recommendations issued in 2003 by a team of experts from the UN Environment Programme (UNEP). The UNEP findings were alarming: after two decades of conflict and drought, Afghanistan had lost nearly all of its wetlands and much of its forests, and its citizens were increasingly at risk for infections and epidemics caused by poor waste management and unequal access to fresh water. [For more on the UNEP findings, see “Environmental Triage in Afghanistan,” EHP 111:A470–A473 (2003).] For two years, Asif Ali Zaidi, UNEP’s program manager in Afghanistan, has worked to help the government respond. UNEP facilitated consultations on the draft legislation with various agencies, citizen groups, and international officials, and funded translations of the draft law into Dari and Pashto, the country’s official languages. Besides NEPA (which emerged from the former Ministry of Irrigation, Water Resources, and Environment), other agencies with key roles under the new law include the Ministry of Justice and the Ministry of Agriculture, Animal Husbandry, and Food. In Afghanistan, more than 80% of the population relies directly on natural resources such as rangelands and water bodies for their livelihood and daily needs, and only 12% of the land is arable. Thus, widespread environmental degradation poses a threat to livelihoods and places the poorest Afghans at particular risk, wrote Zaidi and Belinda Bowling, UNEP’s environmental law expert in Afghanistan, in the Fall 2005 issue of Sustainable Development Law & Policy. Zaidi and Bowling linked environmental issues directly with Afghans’ top concern, security, observing that environmental degradation in Afghanistan—often the consequence of socioeconomic inequities—is a factor contributing to prevalent insecurity. In one example, desperate subsistence farmers displaced by desertification and crop failure are more likely to cultivate poppies as part of the drug trade, which is intrinsically linked to insecurity in Afghanistan. Protecting natural resources in a country lacking basic infrastructure has posed a serious challenge. The National Development Framework, a 2002 map for Afghanistan’s economic development, did not mention the environment, although Zaidi says it was understood as “an important cross-cutting issue.” In 2004, another approach emerged in the Afghanistan National Development Strategy, an Afghan-specific version of the UN Millennium Development Goals couched as a five-year plan. These overlapping schemes have caused confusion among planners, compounded by a lack of baseline data on forest cover, energy use, and other indicators. According to Bowling, the new law will help spur institutional reform and the development of regimens for pollution control and environmental impact assessments, among other things. “Like most fledgling institutions,” she says, “NEPA now requires time to establish itself properly within the new government structure.” UNEP plans to support much of the reform through its Post-Conflict Branch. Hanrahan is cautiously optimistic about the recent developments. Most Afghans, he says, care about their environment. He notes the people have a history of cooperative practices, for example in ancient irrigation systems, adding, “This is where civilization comes from.”

Making Progress on Breast Cancer

For the last two years, scientists across the country have been working together in a highly collaborative effort to uncover the links between exposure to environmental pollutants, puberty, and development of breast cancer. On 10–11 November 2005 the Breast Cancer and the Environment Research Centers (BCERCs), a joint effort of the NIEHS and the National Cancer Institute, came together in Michigan to share what they have accomplished to date. Each center reported on advances made over the past year in their two research components: 1) research on the basic biology of mammary gland development, and 2) epidemiologic studies of how environmental factors affect puberty in girls. The impetus for creation of the centers came from appeals from advocates, who urged the NIH to support a more comprehensive approach to research on the environmental causes of breast cancer. “We wanted a research approach that focused on environmental causes, and we wanted more involvement from the advocates’ perspective,” said Dale Eastman, vice president of the Alamo Breast Cancer Foundation. “The centers represent a great opportunity to conduct transdisciplinary science to explore the problem of breast cancer from many different perspectives, including the valuable perspective of [breast cancer survivor] advocates,” said Robert Hiatt, principal investigator for the BCERC at the University of California, San Francisco, which collaborates with Lawrence Berkeley National Laboratory and serves as the coordinating center for the BCERC network. The other three centers are housed at the Fox Chase Cancer Center in Philadelphia (which collaborates with Mount Sinai School of Medicine in New York and the University of Alabama at Birmingham), the University of Cincinnati in Ohio (which collaborates with Cincinnati Children’s Hospital Medical Center), and Michigan State University in East Lansing. Three important features characterize the BCERC program. First, the four centers work together as a network in which experimental methods are coordinated in order to maximize the pooling and comparison of the data generated. Second, to allow adequate time to track the subjects and collect comprehensive information on the onset and progress of puberty, the BCERCs will be funded for seven years, an unusually long time, given that most NIH grants are funded for a maximum of five years. Third, representatives of breast cancer survivor advocacy organizations are integral members of the centers. The advocate members participate in many aspects of the decision-making processes, collaborate with the Community Outreach and Translation Cores of the centers, and added much to the discussion at the annual meeting.

Note from the Editor: Looking Forward

Vol. 114, No. 1 PerspectivesOpen AccessNote from the Editor: Looking Forward James G. Burkhart James G. Burkhart Search for more papers by this author Published:1 January 2006https://doi.org/10.1289/ehp.114-a13Cited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail With this issue EHP bids a warm goodbye to Tom Goehl, our Editor-in-Chief since October 2001. Tom is a true altruist, always believing that the role of EHP is to impact the human condition by providing a forum for scientific information to be used by researchers, policy makers, and individuals to improve human health around the world. His devotion, drive, and integrity in working toward this goal are unmatched. I have no doubt that Tom will continue to be a dedicated contributor to global environmental health, though he claims it may be from a secluded camping spot far, far away. Farewell and safe journeys!The January 2006 cover introduces a new look for the face of EHP. Over the last few years we have received many compliments on the cover photography and graphic art appearing with each new issue. These images have always been designed to convey a visual link to an environmental health topic in each issue. The new covers will continue in this tradition with some modifications we hope will enhance usability, mainly by providing in the left margin a way for the reader to quickly scan major news and research topics in the issue. The cover titles will also be more descriptive. The Table of Contents will now appear solely inside the journal, leaving the back cover available for announcements or advertisements. As always, we welcome any comments and suggestions you may have.The staff of EHP wishes each of you the very best in the coming year and success in meeting the challenges that will inevitably come our way. As a member of a dynamic global environmental health community, EHP will continually strive to provide you with the best information for improving human and global health.FiguresReferencesRelatedDetailsCited ByJobling S and Tyler C (2006) Introduction: The Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife, Environmental Health Perspectives, 114:Suppl 1, (7-8), Online publication date: 1-Apr-2006. Vol. 114, No. 1 January 2006Metrics About Article Metrics Publication History Originally published1 January 2006Published in print1 January 2006 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Contaminant-induced feminization and demasculinization of nonmammalian vertebrate males in aquatic environments

Many chemicals introduced into the environment by humans adversely affect embryonic development and the functioning of the male reproductive system. It has been hypothesized that these developmental alterations are due to the endocrine-disruptive effects of various environmental contaminants. The endocrine system exhibits an organizational effect on the developing embryo. Thus, a disruption of the normal hormonal signals can permanently modify the organization and future function of the male reproductive system. A wide range of studies examining wildlife either in laboratories or in natural settings have documented alterations in the development of males. These studies have begun to provide the causal relationships between embryonic contaminant exposure and reproductive abnormalities that have been lacking in pure field studies of wild populations. An understanding of the developmental consequences of endocrine disruption in wildlife can lead to new indicators of exposure and a better understanding of the most sensitive life stages as well as the consequences of exposure during these periods.

Endocrine Disrupters in the Aquatic Environment: An Overview

Although a relatively new area of environmental research, the field of endocrine disruption has grown very rapidly, and currently many hundreds, perhaps even a few thousand, papers are published annually on the many different aspects covered by the field. As far as endocrine disruption in wildlife is concerned, most attention has been focused on aquatic organisms, for two reasons. Firstly, the aquatic environment receives most of the pollutants intentionally released into the environment, through effluents from wastewater treatment plants, and secondly because many of the best documented examples of endocrine disruption in wildlife are of partially or completely aquatic species. These two reasons are probably not unconnected, of course. Hence, aquatic organisms can receive continuous exposure to endocrine-disrupting chemicals throughout their lives, albeit usually to low concentrations of these chemicals. Analysis of effluents has identified many of the endocrine-disrupting chemicals present, and shown that these are both natural and man-made, and vary greatly in potency. Most attention has been directed to identifying the main estrogenic chemicals, because many of the effects reported in wildlife appear to be a consequence of ‘feminization’ of males. However, chemical analysis of effluents has also demonstrated that chemicals with other types of endocrine activity are present, such as androgens, anti-androgens, progestagens, etc. The effects (if any, of course) of such chemicals on aquatic organisms are unknown, and largely uninvestigated, presently. Much of the biological research has centred on the effects of estrogenic chemicals, especially to fish. These effects, such as elevated vitellogenin concentrations and intersexuality, have to date been studied almost exclusively at the level of the individual, and hence whether endocrine-disrupting chemicals cause population-level consequences is largely unknown (the undeniable effects of TBT on molluscs, leading to local extinctions, being the exception). It is my opinion that rather too much of the recent research has not advanced our understanding of endocrine disruption a great deal, and we are probably not much further forward now than we were five years or so ago. It is surely time to tackle some of the outstanding, unresolved issues, such as the impact of endocrine disruption at the population level, and the issue of how organisms respond when exposed to complex mixtures of endocrine active chemicals. Such research will not be easy, and will require multidisciplinary teams, including people with expertise in areas not yet involved in the field of endocrine disruption, such as mathematical modellers. However, until such research is done, it will not be possible to decide how important an issue endocrine disruption is to wildlife, and how that importance compares to the other factors adversely affecting wildlife, such as habitat loss, climate change, and the introduction of exotic species and novel diseases.