RESUMO
Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.
Assuntos
Museus , Manejo de Espécimes , Animais , História NaturalRESUMO
Nitrate is heavily used as an agricultural fertilizer and is today a ubiquitous environmental pollutant. Environmental endocrine effects caused by nitrate have received increasing attention over the last 15 years. Nitrate is hypothesized to interfere with thyroid and steroid hormone homeostasis and developmental and reproductive end points. The current review focuses on aquatic ecotoxicology with emphasis on field and laboratory controlled in vitro and in vivo studies. Furthermore, nitrate is just one of several forms of nitrogen that is present in the environment and many of these are quickly interconvertible. Therefore, the focus is additionally confined to the oxidized nitrogen species (nitrate, nitrite and nitric oxide). We reviewed 26 environmental toxicology studies and our main findings are (1) nitrate has endocrine disrupting properties and hypotheses for mechanisms exist, which warrants for further investigations; (2) there are issues determining actual nitrate-speciation and abundance is not quantified in a number of studies, making links to speciation-specific effects difficult; and (3) more advanced analytical chemistry methodologies are needed both for exposure assessment and in the determination of endocrine biomarkers.
Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Nitratos , Nitritos , ReproduçãoRESUMO
This paper describes a novel analytical methodology for the simultaneous determination of absolute and total concentrations of 11 native thyroid hormones and associated metabolites, viz. thyroxine (T4), 3,3', 5-triiodothyronine (T3), 3,3', 5'-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'- diiodothyronine (3,3'-T2), 3-iodothyronine (T1), thyronine (T0), 3-iodothyronamine (T1AM), tetraiodothyroacetic acid (Tetrac), triiodothyroacetic acid (Triac), and diiodothyroacetic acid (Diac), in 50-µL of plasma or serum. The method was optimized using four isotopic labeled surrogate and internal standards in combination with solid-phase extraction and LC-MS/MS. The methodology was further evaluated using amphibian plasma and serum with matrix-matched calibration applied for quantification. Method detection limits are 3.5 pg T4, 1.5 pg T3, 2.9 pg rT3, 1.7 pg 3,3'-T2, 2.3 pg 3,5-T2, and between 0.3 and 7.5 pg for the remaining six metabolites in 50 µL aliquots of blood sera or plasma. Accuracies and repeatabilities for all analytes were between 88 and 103 % and 1.31 and 17.2 %, respectively. Finally, we applied the method on adult frog (Xenopus laevis) plasma and tadpole (Rana (Lithobates) catesbeiana) serum. We observed up to seven different thyroid hormones and associated metabolites in tadpole serum. This method will enable researchers to improve the assessment of thyroid homeostasis and endocrine disruption in animals and humans. Graphical Abstract Quantification of 11 thyroid hormones and metabolites from 50 µL plasma or serum using protein denaturation in combination with solid-phase extraction followed by LC-MS/MS.
Assuntos
Cromatografia Líquida/métodos , Técnica de Diluição de Radioisótopos , Espectrometria de Massas em Tandem/métodos , Hormônios Tireóideos/sangue , Animais , Análise Química do Sangue/métodos , Misturas Complexas/sangue , Rana catesbeiana , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Xenopus laevisRESUMO
The effect of long-term stress on amphibian immunity is not well understood. We modeled a long-term endocrine stress scenario by elevating plasma corticosterone in two species of amphibians and examined effects on white blood cell differentials and innate immune activity. Plasma corticosterone was elevated in American bullfrogs (Lithobates catesbeianus) by surgically implanting corticosterone capsules and in African clawed frogs (Xenopus laevis) by immersion in corticosterone-treated water. To provide a context for our results within endogenous corticosterone fluctuations, diurnal plasma corticosterone cycles were determined. A daily low of corticosterone was observed in X. laevis at 12:00, while a significant pattern was not observed in L. catesbeianus. Elevated plasma corticosterone levels increased the ratio of peripheral neutrophils to lymphocytes, in both species, and decreased eosinophil concentrations in L. catesbeianus over a long-term period. Whole blood oxidative burst generally correlated with neutrophil concentrations, and thus was increased with corticosterone treatment, significantly in L. catesbeianus. In L. catesbeianus, an endogenous response of eosinophils and lymphocytes to implanted empty (sham) capsules was observed, but this effect was attenuated by corticosterone. Peripheral monocyte and basophil concentrations were not significantly altered by corticosterone treatment in either species. Our results show that long-term stress can alter amphibian immune parameters for extended periods and may play a role in susceptibility to disease.
Assuntos
Anti-Inflamatórios/farmacologia , Corticosterona/farmacologia , Sistema Endócrino/efeitos dos fármacos , Rana catesbeiana/fisiologia , Xenopus laevis/fisiologia , Animais , Anti-Inflamatórios/sangue , Células Cultivadas , Corticosterona/sangue , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Imunoensaio , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismoRESUMO
This paper presents the development, optimization, and validation of a LC-MS/MS methodology to determine the concentration of the antifungal drug and fungicide tebuconazole in a controlled exposure study of African clawed frogs (Xenopus laevis). The method is validated on animal tank water and on tissue from exposed and non-exposed adult X. laevis. Using solid-phase extraction (SPE), the analytical method allows for quantification of tebuconazole at concentrations as low as 3.89 pg mL(-1) in 10 mL water samples. Using bead-beating-assisted matrix solid-phase dispersion (MSPD), it was possible to quantify tebuconazole down to 0.63 pg mg(-1) wet weight liver using 150 mg tissue. The deuterated analogue of tebuconazole was used as internal standard, and ensured method accuracy in the range 80.6-99.7% for water and 68.1-109% for tissue samples. The developed method was successfully applied in a 4-week X. laevis repeated-exposure study, revealing high levels of tebuconazole residues in adipose and liver tissue, and with experimental bioconcentration factors up to 18,244 L kg(-1).
Assuntos
Exposição Ambiental/análise , Fígado/química , Espectrometria de Massas/métodos , Extração em Fase Sólida/métodos , Triazóis/análise , Poluentes Químicos da Água/análise , Xenopus laevis/metabolismo , Animais , Bioensaio/métodos , Cromatografia Líquida/métodos , Monitoramento Ambiental/métodos , Triazóis/química , Poluentes Químicos da Água/químicaRESUMO
The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazine-exposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazine-exposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines.
Assuntos
Atrazina/toxicidade , Feminização/induzido quimicamente , Diferenciação Sexual/efeitos dos fármacos , Xenopus laevis/fisiologia , Análise de Variância , Animais , Poluentes Ambientais/toxicidade , Feminino , Feminização/sangue , Feminização/fisiopatologia , Fertilidade/efeitos dos fármacos , Herbicidas/toxicidade , Larva/efeitos dos fármacos , Larva/fisiologia , Laringe/efeitos dos fármacos , Laringe/patologia , Masculino , Comportamento Sexual Animal/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangueRESUMO
The continued presence of gonadotropin-releasing hormone (GnRH) neurons is required for a healthy reproductive lifespan, but factors that maintain postnatal GnRH neurons have not been identified. To begin to understand these factors, we investigated whether 1) fibroblast growth factor (FGF) signaling and 2) interactions with the opposite sex are involved in the maintenance of the postnatal GnRH system. A transgenic mouse model (dnFGFR mouse) with the targeted expression of a dominant-negative FGF receptor (dnFGFR) in GnRH neurons was used to examine the consequence of FGF signaling deficiency on postnatal GnRH neurons. Male dnFGFR mice suffered a significant loss of postnatal GnRH neurons within the first 100 days of life. Interestingly, this loss was reversed after cohabitation with female, but not male, mice for 300-550 days. Along with a rescue in GnRH neuron numbers, opposite-sex housing in dnFGFR males also increased hypothalamic GnRH peptide levels, promoted a more mature GnRH neuronal morphology, facilitated litter production, and enhanced testicular morphology. Last, mice hypomorphic for FGFR3 exhibited a similar pattern of postnatal GnRH neuronal loss as dnFGFR males, suggesting FGF signaling acts, in part, through FGFR3 to enhance the maintenance of the postnatal GnRH system. In summary, we have shown that FGF signaling is required for the continued presence of postnatal GnRH neurons. However, this requirement is not absolute, since sexual interactions can compensate for defects in FGFR signaling, thereby rescuing the declining GnRH system. This suggests the postnatal GnRH system is highly plastic and capable of responding to environmental stimuli throughout adult life.
Assuntos
Envelhecimento , Fator 3 de Crescimento de Fibroblastos/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Neurônios/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Animais , Contagem de Células , Heterozigoto , Hipotálamo/citologia , Hipotálamo/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Degeneração Neural/etiologia , Degeneração Neural/prevenção & controle , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptores LHRH/metabolismo , Comportamento Sexual Animal , Transmissão Sináptica , Testículo/citologia , Testículo/crescimento & desenvolvimento , Testículo/metabolismoRESUMO
Endocrine research in animals often entails exogenous hormone administration. Special issues arise when developing administration protocols for hormones with circadian and seasonal periodicity. This article reviews various methods for the exogenous administration of hormones with such periodicities by focusing on melatonin. We discuss that methodological variations across studies can affect experimental results. Melatonin administration techniques used in vertebrates includes infusion pumps, beeswax pellets, oral administration, injections, SILASTIC capsules, osmotic pumps, transdermal delivery, beads, and sponges.
Assuntos
Aves/fisiologia , Ritmo Circadiano/efeitos dos fármacos , Mamíferos/fisiologia , Melatonina/administração & dosagem , Pesquisa , Administração Cutânea , Administração Oral , Animais , Cápsulas/administração & dosagem , Feminino , Injeções , Masculino , Estações do AnoRESUMO
BACKGROUND: Atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. The mechanism involves the inhibition of phosphodiesterase and subsequent elevation of cAMP. METHODS: We compared steroidogenic factor 1 (SF-1) expression in atrazine responsive and non-responsive cell lines and transfected SF-1 into nonresponsive cell lines to assess SF-1's role in atrazine-induced aromatase. We used a luciferase reporter driven by the SF-1-dependent aromatase promoter (ArPII) to examine activation of this promoter by atrazine and the related simazine. We mutated the SF-1 binding site to confirm the role of SF-1. We also examined effects of 55 other chemicals. Finally, we examined the ability of atrazine and simazine to bind to SF-1 and enhance SF-1 binding to ArPII. RESULTS: Atrazine-responsive adrenal carcinoma cells (H295R) expressed 54 times more SF-1 than nonresponsive ovarian granulosa KGN cells. Exogenous SF-1 conveyed atrazine-responsiveness to otherwise nonresponsive KGN and NIH/3T3 cells. Atrazine induced binding of SF-1 to chromatin and mutation of the SF-1 binding site in ArPII eliminated SF-1 binding and atrazine-responsiveness in H295R cells. Out of 55 chemicals examined, only atrazine, simazine, and benzopyrene induced luciferase via ArPII. Atrazine bound directly to SF-1, showing that atrazine is a ligand for this "orphan" receptor. CONCLUSION: The current findings are consistent with atrazine's endocrine-disrupting effects in fish, amphibians, and reptiles; the induction of mammary and prostate cancer in laboratory rodents; and correlations between atrazine and similar reproductive cancers in humans. This study highlights the importance of atrazine as a risk factor in endocrine disruption in wildlife and reproductive cancers in laboratory rodents and humans.
Assuntos
Aromatase/metabolismo , Atrazina/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Fator Esteroidogênico 1/metabolismo , Análise de Variância , Animais , Aromatase/genética , Sítios de Ligação/genética , Western Blotting , Linhagem Celular Tumoral , Primers do DNA , Humanos , Ligantes , Luciferases/metabolismo , Camundongos , Mutação/genética , Regiões Promotoras Genéticas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Simazina/metabolismoRESUMO
Amphibian populations are declining globally at an alarming rate. Pesticides are among a number of proposed causes for these declines. Although a sizable database examining effects of pesticides on amphibians exists, the vast majority of these studies focus on toxicological effects (lethality, external malformations, etc.) at relatively high doses (parts per million). Very few studies focus on effects such as endocrine disruption at low concentrations. Further, most studies examine exposures to single chemicals only. The present study examined nine pesticides (four herbicides, two fungicides, and three insecticides) used on cornfields in the midwestern United States. Effects of each pesticide alone (0.1 ppb) or in combination were examined. In addition, we also examined atrazine and S-metolachlor combined (0.1 or 10 ppb each) and the commercial formulation Bicep II Magnum, which contains both of these herbicides. These two pesticides were examined in combination because they are persistent throughout the year in the wild. We examined larval growth and development, sex differentiation, and immune function in leopard frogs (Rana pipiens). In a follow-up study, we also examined the effects of the nine-compound mixture on plasma corticosterone levels in male African clawed frogs (Xenopus laevis). Although some of the pesticides individually inhibited larval growth and development, the pesticide mixtures had much greater effects. Larval growth and development were retarded, but most significantly, pesticide mixtures negated or reversed the typically positive correlation between time to metamorphosis and size at metamorphosis observed in controls: exposed larvae that took longer to metamorphose were smaller than their counterparts that metamorphosed earlier. The nine-pesticide mixture also induced damage to the thymus, resulting in immunosuppression and contraction of flavobacterial meningitis. The study in X. laevis revealed that these adverse effects may be due to an increase in plasma levels of the stress hormone corticosterone. Although it cannot be determined whether all the pesticides in the mixture contribute to these adverse effects or whether some pesticides are effectors, some are enhancers, and some are neutral, the present study revealed that estimating ecological risk and the impact of pesticides on amphibians using studies that examine only single pesticides at high concentrations may lead to gross underestimations of the role of pesticides in amphibian declines.
Assuntos
Anfíbios , Disruptores Endócrinos/toxicidade , Praguicidas/toxicidade , Animais , Tamanho Corporal/efeitos dos fármacos , Corticosterona/sangue , Ecossistema , Disruptores Endócrinos/farmacocinética , Exposição Ambiental , Feminino , Flavobacterium/patogenicidade , Cadeia Alimentar , Gônadas/citologia , Gônadas/efeitos dos fármacos , Masculino , Metamorfose Biológica/efeitos dos fármacos , Praguicidas/farmacocinética , Rana pipiens , Medição de Risco , Diferenciação Sexual , Desenvolvimento Sexual/efeitos dos fármacos , Timo/citologia , Timo/efeitos dos fármacos , Timo/imunologia , Fatores de Tempo , Xenopus laevisRESUMO
Atrazine is a potent endocrine disruptor that both chemically castrates and feminizes male amphibians. It depletes androgens in adult frogs and reduces androgen-dependent growth of the larynx in developing male larvae. It also disrupts normal gonadal development and feminizes the gonads of developing males. Gonadal malformations induced by atrazine include hermaphrodites and males with multiple testes [single sex polygonadism (SSP)], and effects occur at concentrations as low as 0.1 ppb (microg/L). Here, we describe the frequencies at which these malformations occur and compare them with morphologies induced by the estrogen, 17beta-estradiol (E2) , and the antiandrogen cyproterone acetate, as a first step in testing the hypothesis that the effects of atrazine are a combination of demasculinization and feminization. The various forms of hermaphroditism did not occur in controls. Nonpigmented ovaries, which occurred at relatively high frequencies in atrazine-treated larvae, were found in four individuals out of more than 400 controls examined (1%). Further, we show that several types of gonadal malformations (SSP and three forms of hermaphroditism) are produced by E2 exposure during gonadal differentiation, whereas a final morphology (nonpigmented ovaries) appears to be the result of chemical castration (disruption of androgen synthesis and/or activity) by atrazine. These experimental findings suggest that atrazine-induced gonadal malformations result from the depletion of androgens and production of estrogens, perhaps subsequent to the induction of aromatase by atrazine, a mechanism established in fish, amphibians, reptiles, and mammals (rodents and humans).
Assuntos
Atrazina/toxicidade , Acetato de Ciproterona/farmacologia , Estradiol/farmacologia , Feminização/induzido quimicamente , Gônadas/anormalidades , Xenopus laevis/anormalidades , Antagonistas de Androgênios/farmacologia , Animais , Estudos Transversais , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Transtornos do Desenvolvimento Sexual/patologia , Feminino , Feminização/epidemiologia , Gônadas/efeitos dos fármacos , Masculino , Metamorfose Biológica/efeitos dos fármacos , Modelos Biológicos , Diferenciação Sexual/efeitos dos fármacos , Diferenciação Sexual/fisiologiaRESUMO
A 27-day controlled exposure study of adult male African clawed frogs (Xenopus laevis) was conducted to examine the mechanism by which tebuconazole may disrupt steroidogenesis. The fungicide was measured by LC-MS/MS in tank water and in target tissues (adipose, kidney, liver, and brain), and we observed tissue-specific bioconcentration with BCF up to 238. Up to 10 different steroid hormones were quantified in gonads using LC-MS/MS and in plasma using GC-MS/MS and a radioimmunoassay was performed for further measurement of androgens. In order to assess whether effects increased with exposure or animals adapted to the xenobiotic, blood samples were collected 12 days into the study and at termination (day 27). After 12 days of exposure to 100 and 500µgL(-1) tebuconazole, plasma levels of testosterone (T) and dihydrotestosterone (DHT) were increased, while plasma 17ß-estradiol (E2) concentrations were greatly reduced. Exposure to 0.1µgL(-1), on the other hand, resulted in decreased levels of T and DHT, with no effects observed for E2. After 27 days of exposure, effects were no longer observed in circulating androgen levels while the suppressive effect on E2 persisted in the two high-exposure groups (100 and 500µgL(-1)). Furthermore, tebuconazole increased gonadal concentrations of T and DHT as well as expression of the enzyme CYP17 (500µgL(-1), 27 days). These results suggest that tebuconazole exposure may supress the action of CYP17 at the lowest exposure (0.1µgL(-1)), while CYP19 suppression dominates at higher exposure concentrations (increased androgens and decreased E2). Increased androgen levels in plasma half-way into the study and in gonads at termination may thus be explained by compensatory mechanisms, mediated through increased enzymatic expression, as prolonged exposure had no effect on circulating androgen levels.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Triazóis/toxicidade , Xenopus laevis/fisiologia , Androgênios/metabolismo , Animais , Aromatase/genética , Aromatase/metabolismo , Di-Hidrotestosterona/metabolismo , Estradiol/sangue , Estradiol/genética , Estradiol/metabolismo , Fungicidas Industriais/toxicidade , Gônadas/química , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Masculino , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Espectrometria de Massas em Tandem , Testosterona/metabolismo , Poluentes Químicos da Água/toxicidadeAssuntos
Academias e Institutos , Racismo , Universidades , Engenharia , Humanos , Matemática , Ciência , Tecnologia , Estados UnidosRESUMO
Atrazine is the most commonly used herbicide in the United States and probably the world. Atrazine contamination is widespread and can be present in excess of 1.0 ppb even in precipitation and in areas where it is not used. In the current study, we showed that atrazine exposure (> or = to 0.1 ppb) resulted in retarded gonadal development (gonadal dysgenesis) and testicular oogenesis (hermaphroditism) in leopard frogs (Rana pipiens). Slower developing males even experienced oocyte growth (vitellogenesis). Furthermore, we observed gonadal dysgenesis and hermaphroditism in animals collected from atrazine-contaminated sites across the United States. These coordinated laboratory and field studies revealed the potential biological impact of atrazine contamination in the environment. Combined with reported similar effects in Xenopus laevis, the current data raise concern about the effects of atrazine on amphibians in general and the potential role of atrazine and other endocrine-disrupting pesticides in amphibian declines.
Assuntos
Atrazina/efeitos adversos , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Transtornos do Desenvolvimento Sexual/veterinária , Exposição Ambiental , Herbicidas/efeitos adversos , Rana pipiens/anatomia & histologia , Poluentes Químicos da Água/efeitos adversos , Animais , Atrazina/administração & dosagem , Sistema Endócrino/efeitos dos fármacos , Monitoramento Ambiental , Feminino , Gônadas/crescimento & desenvolvimento , Herbicidas/administração & dosagem , Masculino , Diferenciação Sexual , Estados UnidosAssuntos
Atrazina/toxicidade , Neoplasias da Mama/induzido quimicamente , Indústria Farmacêutica , Herbicidas/toxicidade , Neoplasias da Próstata/induzido quimicamente , Animais , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Neoplasias da Próstata/prevenção & controleRESUMO
Extensive corn production in the midwestern United States has physically eliminated or fragmented vast areas of historical amphibian habitat. Midwestern corn farmers also apply large quantities of fertilizers and herbicides, which can cause direct and indirect effects on amphibians. Limited field research regarding the statuses of midwestern amphibian populations near areas of corn production has left resource managers, conservation planners, and other stakeholders needing more information to improve conservation strategies and management plans. We repeatedly sampled amphibians in wetlands in four conservation areas along a gradient of proximity to corn production in Illinois, Iowa, Minnesota, and Wisconsin from 2002 to 2005 and estimated site occupancy. We measured frequencies of gross physical deformities in recent metamorphs and triazine concentrations in the water at breeding sites. We also measured trematode infection rates in kidneys of recently metamorphosed Lithobates pipiens collected from nine wetlands in 2003 and 2004. We detected all possible amphibian species in each study area. The amount of nearby row crops was limited in importance as a covariate for estimating site occupancy. We observed deformities in <5% of metamorphs sampled and proportions were not associated with triazine concentrations. Trematode infections were high in metamorphs from all sites we sampled, but not associated with site triazine concentrations, except perhaps for a subset of sites sampled in both years. We detected triazines more often and in higher concentrations in breeding wetlands closer to corn production. Triazine concentrations increased in floodplain wetlands as water levels rose after rainfall and were similar among lotic and lentic sites. Overall, our results suggest amphibian populations were not faring differently among these four conservation areas, regardless of their proximity to corn production, and that the ecological dynamics of atrazine exposure were complex.
Assuntos
Anfíbios/fisiologia , Atrazina/toxicidade , Conservação dos Recursos Naturais , Exposição Ambiental/análise , Anfíbios/parasitologia , Animais , Cruzamento , Coleta de Dados , Ensaio de Imunoadsorção Enzimática , Geografia , Herbicidas/toxicidade , Concentração de Íons de Hidrogênio , Masculino , Metamorfose Biológica/efeitos dos fármacos , Meio-Oeste dos Estados Unidos , Dinâmica Populacional , Infecções por Trematódeos/parasitologia , Triazinas/toxicidade , Poluentes Químicos da Água/toxicidade , Áreas Alagadas , Zea mays/crescimento & desenvolvimentoRESUMO
For years, scientists from various disciplines have studied the effects of endocrine disrupting chemicals (EDCs) on the health and wellbeing of humans and wildlife. Some studies have specifically focused on the effects of low doses, i.e. those in the range that are thought to be safe for humans and/or animals. Others have focused on the existence of non-monotonic dose-response curves. These concepts challenge the way that chemical risk assessment is performed for EDCs. Continued discussions have clarified exactly what controversies and challenges remain. We address several of these issues, including why the study and regulation of EDCs should incorporate endocrine principles; what level of consensus there is for low dose effects; challenges to our understanding of non-monotonicity; and whether EDCs have been demonstrated to produce adverse effects. This discussion should result in a better understanding of these issues, and allow for additional dialog on their impact on risk assessment.
Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Animais , Tomada de Decisões , Relação Dose-Resposta a Droga , Disruptores Endócrinos/administração & dosagem , Endocrinologia , Poluentes Ambientais/administração & dosagem , Regulamentação Governamental , Humanos , Medição de Risco/legislação & jurisprudênciaRESUMO
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.
Assuntos
Mama/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Anfíbios/crescimento & desenvolvimento , Animais , Animais Selvagens , Atrazina/toxicidade , Compostos Benzidrílicos , Dioxinas/toxicidade , Relação Dose-Resposta a Droga , Exposição Ambiental , Feminino , Herbicidas/toxicidade , Humanos , Masculino , Percloratos/toxicidade , Fenóis/toxicidade , Próstata/efeitos dos fármacos , Desenvolvimento Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , GêmeosRESUMO
Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called "Hill criteria" (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause-effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of atrazine on male development are consistent across all vertebrate classes examined and we present a state of the art summary of the mechanisms by which atrazine acts as an endocrine disruptor to produce these effects. Atrazine demasculinizes male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, and reptiles. These effects are strong (statistically significant), consistent across vertebrate classes, and specific. Reductions in androgen levels and the induction of estrogen synthesis - demonstrated in fish, amphibians, reptiles, and mammals - represent plausible and coherent mechanisms that explain these effects. Biological gradients are observed in several of the cited studies, although threshold doses and patterns vary among species. Given that the effects on the male gonads described in all of these experimental studies occurred only after atrazine exposure, temporality is also met here. Thus the case for atrazine as an endocrine disruptor that demasculinizes and feminizes male vertebrates meets all nine of the "Hill criteria".
Assuntos
Atrazina/toxicidade , Feminização/induzido quimicamente , Praguicidas/toxicidade , Testículo/efeitos dos fármacos , Animais , Disruptores Endócrinos/toxicidade , Estrogênios/biossíntese , Estrogênios/sangue , Herbicidas/toxicidade , Humanos , Masculino , Camundongos , Ratos , Testículo/crescimento & desenvolvimento , Testículo/patologia , Testosterona/biossíntese , Testosterona/sangue , Poluentes Químicos da Água/toxicidadeRESUMO
I am honored to receive the E. E. Just Award for 2010. In my invited essay, I have opted to discuss the state of diversity in the biological sciences with some recommendations for moving forward toward a more positive and inclusive academy. The need to develop cohorts of minority scientists as support groups and to serve as role models within our institutions is stressed, along with the need to ensure that minority scientists are truly included in all aspects of the academy. It is imperative that we increase our efforts to prepare for the unique challenges that we will face as the United States approaches a "majority minority" population in the next 50 years.