Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay
01 Aug 2000-Journal of Health Science (The Pharmaceutical Society of Japan)-Vol. 46, Iss: 4, pp 282-298
TL;DR: A simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators to test the estrogenic activity of chemicals.
Abstract: One of the urgent tasks in understanding endocrine disruptors (EDs) is to compile a list of suspected substances among the huge number of chemicals by using the screening test method. We developed a simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators. To date, we have tested the estrogenic activity of more than 500 chemicals including natural substances, medicines, pesticides, and industrial chemicals. 64 compounds were evaluated as positive, and most of these demonstrated a common structure; phenol with a hydrophobic moiety at the para-position without bulky groups at the ortho-position. These results are expected to facilitate further risk assessment of chemicals.
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01 Apr 2012
TL;DR: A Toxicological Profile for 1,4-Dioxane, Draft for Public Comment was released in October 2007 and supersedes any previously released draft or final profile, which reflects ATSDR's assessment of all relevant toxicologic testing and information that has been peer-reviewed.
Abstract: A Toxicological Profile for 1,4-Dioxane, Draft for Public Comment was released in October 2007. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at: FOREWORD This toxicological profile is prepared in accordance with guidelines* developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the toxic substances each profile describes. Each peer-reviewed profile identifies and reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is also presented but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profiles focus on health and toxicologic information; therefore, each toxicological profile begins with a public health statement that describes, in nontechnical language, a substance's relevant toxicological properties. Following the public health statement is information concerning levels of significant human exposure and, where known, significant health effects. A health effects summary describes the adequacy of information to determine a substance's health effects. ATSDR identifies data needs that are significant to protection of public health. Each profile: (A) Examines, summarizes, and interprets available toxicologic information and epidemiologic evaluations on a toxic substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; (B) Determines whether adequate information on the health effects of each substance is available or being developed to determine levels of exposure that present a significant risk to human health of acute, subacute, and chronic health effects; and (C) Where appropriate, identifies toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans. The principal audiences for the toxicological profiles are federal, state, and local health professionals; interested private sector organizations and groups; and members of the public. This profile reflects ATSDR's assessment of all relevant toxicologic testing and information that has been peer-reviewed. Staff of the Centers for Disease Control and Prevention and other federal scientists also have reviewed the profile. In addition, …
34 citations
TL;DR: The data suggest that OECD test guideline TG455 may be useful as a screening tool for potential endocrine disruptors.
Abstract: Screening of estrogenic activity on dichloro diphenyl trichloroethane (DDT), dichloro diphenyl dichloro ethylene (DDE), dieldrin, heptachlor, aldrin, chlordane, lindane, polybrominated diphenyl ethers (PBDE) and parabens was compared using Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455). The estrogenic activity of DDT was 58,000-fold (PC50, 1.67 × 10(-6) M) less than 17β-estradiol(E2) (PC50, 2.88 × 10(-11) M) but DDE, dieldrin, heptachlor, aldrin, chlordane, lindane and PBDE did not show any estrogenic activity in this assay system. In the case of paraben compounds, the rank of relative transcriptional activation (logRTA) was butyl paraben -1.63752 (PC50, 1.25 × 10(-7)M) > isobutyl paraben -2.34008 (PC50, 6.3 × 10(-7)M) > ethyl paraben -2.64016 (PC50, 1.26 × 10(-6) M) > isopropyl paraben -2.73993 (PC50, 1.58 × 10(-6)M) > propyl paraben -2.84164 (PC50, 2.0 × 10(-6) M). Our data suggest that OECD test guideline TG455 may be useful as a screening tool for potential endocrine disruptors.
34 citations
TL;DR: The constructed MLR-QSAR model has been statistically validated for its predictive power, and can be proposed as a preliminary evaluative method to screen/prioritize estrogens according to their integrated estrogen activity, just starting from molecular structure.
33 citations
TL;DR: The medaka extended one‐generation test (MEOGRT) was developed as a multigenerational toxicity test for chemicals, particularly endocrine‐disrupting chemicals, and results concerning branched isomer mixtures of 4‐nonylphenol suggest that NP may be affecting fish populations.
Abstract: The medaka extended one-generation test (MEOGRT) was developed as a multigenerational toxicity test for chemicals, particularly endocrine-disrupting chemicals. Briefly, 3 generations of Japanese medaka (Oryzias latipes) are exposed to a chemical over a 20-wk period: 3 wk in the parental generation (F0), 15 wk in the first generation (F1), and 2 wk in the second generation (F2). The present study reports the first MEOGRT results concerning branched isomer mixtures of 4-nonylphenol (NP). Adult F0 medaka exposed to NP at 5 actual concentrations (1.27, 2.95, 9.81, 27.8, 89.4 µg/L) were unaffected in terms of reproduction, although vitellogenin in the male liver was increased dose-dependently at concentration of 2.95 µg/L and higher. In F1, in contrast, total egg (fecundity), fertile egg, and fertility decreased as NP increased; lowest-observed-effect concentrations (LOECs) for total egg, fertile egg, and fertility were 1.27, 1.27, 27.8 µg/L, respectively. In F1, but not in F0, secondary sex characteristics (i.e., anal fin papillae in males) were suppressed at 27.8 µg/L NP. Vitellogenin induction in adult male fish was slightly weaker in F1 than it was in F0, however. Gonadal sex abnormality and sex reversal occurred at 27.8 and 89.4 µg/L NP in F1 subadults. At 89.4 µg/L NP, all genotypic F1 males in breeding pairs had female phenotype, and some even demonstrated spawning. Concentrations of NP lower than 89.4 µg/L did not affect F2 survival or hatching. The highest detected NP level in environmental freshwater in Japan was approximately a half of the LOEC (1.27 µg/L for F1 fecundity); in other countries, however, environmental concentrations above the LOEC are reported, suggesting that NP may be affecting fish populations. Environ Toxicol Chem 2017;36:3254-3266. © 2017 SETAC.
33 citations
Cites methods from "Estrogenic Activities of 517 Chemic..."
...84852-15-3), as suggested by the VTG assay using rainbow trout [22], the 2-hybrid assay [20], and the MVLN transcriptional activation assay [21]....
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TL;DR: Molecular docking and quantitative structure-activity relationship (QSAR) were used to understand the relationship between molecular structural features and estrogenic activity, and to predict the binding affinity of PAHs to estrogen receptor α (ERα).
33 citations
Cites background or methods from "Estrogenic Activities of 517 Chemic..."
...A common structure of estrogenic compounds is a phenol basic structure with a hydrophobic moiety at the para-position and no bulky group at the ortho-position (Nishihara et al., 2000)....
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...Nishihara et al. (2000) tested 12 HO-BaPs isomers (1- through 12- HO-BaPs) using the competition binding assay to ERa, and found that 1-, 2-, 3-, and 9-HO-BaPs were estrogenic and 8-HO-BaPs was antiestrogenic....
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References
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01 Jan 1996
TL;DR: The cause of disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure, is traced to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system.
Abstract: For years, scientists have noticed disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure. Humans are not immune either, with sperm counts dropping by as much as 50% in recent decades and with women seeing a rise in hormone-related cancers, endometriosis and other disorders. This book traces the cause of these aberrations and diseases to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system. The conclusions are as obvious as they are inescapable - unless we make vital changes in the way we manufacture and employ the artefacts of our "good life", there will be no life at all.
917 citations