Predictive Modeling of Thyroid Hormone Disruption and Investigation of Potential Biomarkers of Chemical Exposure

Predictive Modeling of Thyroid Hormone Disruption and Investigation of Potential Biomarkers of Chemical Exposure PDF Author: Jennifer Lynn Flippin
Publisher:
ISBN:
Category :
Languages : en
Pages : 95

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Book Description
Keywords: mixture modeling, thyroid hormone disruption.

Predictive Modeling of Thyroid Hormone Disruption and Investigation of Potential Biomarkers of Chemical Exposure

Predictive Modeling of Thyroid Hormone Disruption and Investigation of Potential Biomarkers of Chemical Exposure PDF Author: Jennifer Lynn Flippin
Publisher:
ISBN:
Category :
Languages : en
Pages : 95

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Book Description
Keywords: mixture modeling, thyroid hormone disruption.

Predictive Modeling of Thyroid Hormone Disruption and Investigation of Potential Biomarkers of Chemical Exposure

Predictive Modeling of Thyroid Hormone Disruption and Investigation of Potential Biomarkers of Chemical Exposure PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
Humans and wildlife are exposed to thyroid hormone disrupting chemicals in their environments. These exposures often occur as complex mixtures of xenobiotics with similar and dissimilar modes of action. This research tested the hypothesis that serum thyroxine (T4) concentrations in rodents exposed to a mixture of chemicals with two distinct modes of action (enhancers of T4 hepatic metabolism and inhibitors of thyroidal hormone synthesis) could be best predicted by a model of integrated addition. Female Long-Evans rats, 23 days of age, were dosed with dilutions of a mixture of 18 polyhalogenated aromatic hydrocarbons (dioxins, dibenzofurans, and polychlorinated biphenyls) and a mixture of three pesticides (pronamide, mancozeb, and thiram) for four consecutive days. Serum was collected 24 hours after the last exposure and T4 concentrations were measured by RIA. Animals exposed to the highest dose of the mixture experienced a 45% decrease in serum T4. Three additivity model predictions (dose addition, effect addition, and integrated addition) were generated and compared. The response to the mixture was best modeled by integrated addition in which responses to the pesticides and polyhalogenated aromatic hydrocarbons were separately evaluated according to dose additivity, and the response of the two groups of chemicals were summed according to effect additivity. The response to the mixture was also well-predicted by a dose addition model. These results lead to a clearer understanding of thyroid hormone disruption by a complex mixture and show that models are able to accurately predict the response of T4 to a mixture of endocrine disruptors. Thiram, mancozeb, and pronamide inhibit thyroid hormone production in the thyroid gland. These hormone decreases may be associated with altered expression of thyroidal genes. It was hypothesized that exposure to TH synthesis inhibitors would result in altered expression of mRNA of PAX-8, Hex, Tg, NIS, and/or TPO in the thyroid gland.

How Tobacco Smoke Causes Disease

How Tobacco Smoke Causes Disease PDF Author: United States. Public Health Service. Office of the Surgeon General
Publisher:
ISBN:
Category : Government publications
Languages : en
Pages : 728

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Book Description
This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

Principles of Endocrinology and Hormone Action

Principles of Endocrinology and Hormone Action PDF Author: Antonino Belfiore
Publisher: Springer
ISBN: 9783319446745
Category : Medical
Languages : en
Pages : 0

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Book Description
This volume provides comprehensive coverage of the current knowledge of the physiology of the endocrine system and hormone synthesis and release, transport, and action at the molecular and cellular levels. It presents essential as well as in-depth information of value to both medical students and specialists in Endocrinology, Gynecology, Pediatrics, and Internal Medicine. Although it is well established that the endocrine system regulates essential functions involved in growth, reproduction, and homeostasis, it is increasingly being recognized that this complex regulatory system comprises not only hormones secreted by the classic endocrine glands but also hormones and regulatory factors produced by many organs, and involves extensive crosstalk with the neural and immune system. At the same time, our knowledge of the molecular basis of hormone action has greatly improved. Understanding this complexity of endocrine physiology is crucial to prevent endocrine disorders, to improve the sensitivity of our diagnostic tools, and to provide the rationale for pharmacological, immunological, or genetic interventions. It is such understanding that this book is designed to foster.

Endocrine Disruption and Human Health

Endocrine Disruption and Human Health PDF Author: Philippa D. Darbre
Publisher: Academic Press
ISBN: 0128011203
Category : Medical
Languages : en
Pages : 390

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Book Description
Endocrine Disruption and Human Health starts with an overview of what endocrine disruptors are, the issues surrounding them, and the source of these chemicals in the ecosystem. This is followed by an overview of the mechanisms of action and assay systems. The third section includes chapters written by specialists on different aspects of concern for the effects of endocrine disruption on human health. Finally, the authors consider the risk assessment of endocrine disruptors and the pertinent regulation developed by the EU, the US FDA, as well as REACH and NGOs. The book has been written for researchers and research clinicians interested in learning about the actions of endocrine disruptors and current evidence justifying concerns for human health but is useful for those approaching the subject for the first time, graduate students, and advanced undergraduate students. Provides readers with access to a range of information from the basic mechanisms and assays to cutting-edge research investigating concerns for human health Presents a comprehensive, translational look at all aspects of endocrine disruption and its effects on human health Offers guidance on the risk assessment of endocrine disruptors and current relevant regulatory considerations

Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals

Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals PDF Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309458625
Category : Science
Languages : en
Pages : 423

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Book Description
To safeguard public health, the US Environmental Protection Agency (EPA) must keep abreast of new scientific information and emerging technologies so that it can apply them to regulatory decision-making. For decades the agency has dealt with questions about what animal-testing data to use to make predictions about human health hazards, how to perform dose-response extrapolations, how to identify and protect susceptible subpopulations, and how to address uncertainties. As alternatives to traditional toxicity testing have emerged, the agency has been faced with additional questions about how to incorporate data from such tests into its chemical assessments and whether such tests can replace some traditional testing methods. Endocrine active chemicals (EACs) have raised concerns that traditional toxicity-testing protocols might be inadequate to identify all potential hazards to human health because they have the ability to modulate normal hormone function, and small alterations in hormone concentrations, particularly during sensitive life stages, can have lasting and significant effects. To address concerns about potential human health effects from EACs at low doses, this report develops a strategy to evaluate the evidence for such low-dose effects.

Endocrine-Disrupting Chemicals

Endocrine-Disrupting Chemicals PDF Author: Andrea C. Gore
Publisher: Springer Science & Business Media
ISBN: 159745107X
Category : Medical
Languages : en
Pages : 361

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Book Description
This book provides comprehensive coverage of the three most important themes in the field of Endocrine Disrupting Chemicals (EDC) research: the basic biology of EDCs, particularly their effects on reproductive systems; EDC effects on humans and wildlife, including biomedical considerations; and potential interventions and practical advice for dealing with the problem of EDCs.

OECD Guidelines for the Testing of Chemicals, Section 2 Test No. 231: Amphibian Metamorphosis Assay

OECD Guidelines for the Testing of Chemicals, Section 2 Test No. 231: Amphibian Metamorphosis Assay PDF Author: OECD
Publisher: OECD Publishing
ISBN: 9264076247
Category :
Languages : en
Pages : 33

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Book Description
This Test Guideline describes an amphibian metamorphosis assay intended to screen substances which may interfere with the normal functioning of the hypothalamo-pituitary-thyroid axis. The assay was validated with the species Xenopus laevis, which is ...

Ecotoxicology of Amphibians and Reptiles

Ecotoxicology of Amphibians and Reptiles PDF Author: Donald W. Sparling
Publisher: CRC Press
ISBN: 1420064177
Category : Science
Languages : en
Pages : 946

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Book Description
Building on the success of its popular predecessor, the second edition of Ecotoxicology of Amphibians and Reptiles presents newly available findings on the species that are important environmental indicators. This new edition covers nearly twice as many topics as the first, including recent developments in the ecotoxicology of amphibians and reptil

Hormonally Active Agents in the Environment

Hormonally Active Agents in the Environment PDF Author: National Research Council
Publisher: National Academies Press
ISBN: 0309064198
Category : Science
Languages : en
Pages : 453

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Book Description
Some investigators have hypothesized that estrogens and other hormonally active agents found in the environment might be involved in breast cancer increases and sperm count declines in humans as well as deformities and reproductive problems seen in wildlife. This book looks in detail at the science behind the ominous prospect of "estrogen mimics" threatening health and well-being, from the level of ecosystems and populations to individual people and animals. The committee identifies research needs and offers specific recommendations to decision-makers. This authoritative volume: Critically evaluates the literature on hormonally active agents in the environment and identifies known and suspected toxicologic mechanisms and effects of fish, wildlife, and humans. Examines whether and how exposure to hormonally active agents occursâ€"in diet, in pharmaceuticals, from industrial releases into the environmentâ€"and why the debate centers on estrogens. Identifies significant uncertainties, limitations of knowledge, and weaknesses in the scientific literature. The book presents a wealth of information and investigates a wide range of examples across the spectrum of life that might be related to these agents.