Endocrine disrupting chemicals research program of the U.S. Environmental Protection Agency: summary of a peer-review report.

At the request of the U.S. Environmental Protection Agency (EPA) Office of Research and Development, a subcommittee of the Board of Scientific Counselors Executive Committee conducted an independent and open peer review of the Endocrine Disrupting Chemicals Research Program (EDC Research Program) of the U.

Human consumption of methyleugenol and its elimination from serum.

Under a mandate from the U.S. Congress, the National Toxicology Program (NTP) of the U.

TCDD-mediated alterations in the AhR-dependent pathway in Seveso, Italy, 20 years after the accident.

Approximately 20 years after the Seveso, Italy, accident we conducted a population-based study to evaluate the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on cancer using mechanistically based biomarkers of dioxin response in humans. TCDD toxic effects are mediated by the aryl hydrocarbon receptor (AhR). We studied the AhR-dependent pathway in lymphocytes from 62 subjects randomly sampled from the highest exposed zones and 59 subjects from the surrounding non-contaminated area, frequency matched for age, gender and smoking.

Serum hormone levels in humans with low serum concentrations of 2,3,7,8-TCDD.

We measured current serum hormone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 37 men who sprayed 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in the State of Victoria, Australia. TCDD levels were consistently significantly inversely related to prolactin levels in all analyses. In correlation analyses, TCDD levels were also inversely related to triiodothyronine (T3), thyroid-stimulating hormone (TSH), and testosterone levels, and positively associated with glucagon levels.

Two-year angiographic follow-up of intracoronary Sr90 therapy for restenosis prevention after balloon angioplasty.

Background: Postcoronary angioplasty vascular brachytherapy (VBT) has emerged as a successful intervention for restenosis prevention in some clinical scenarios. Longer-term follow-up after VBT in de novo nonstented lesions has not been reported.

Methods And Results: Thirty patients treated with post-percutaneous transluminal coronary angioplasty (PTCA) VBT with Sr90 underwent clinical and angiographic follow-up at 6 and 24 months.

Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review.

At the request of the U.S. Environmental Protection Agency (U.

Disproportionation of Ag(II) to Ag(I) and Ag(III) in Fluoride Systems and Syntheses and Structures of (AgF(+))(2)AgF(4)(-)MF(6)(-) Salts (M = As, Sb, Pt, Au, Ru).

Interaction of Ag(+) salts in anhydrous liquid hydrogen fluoride, aHF, with AgF(4)(-) salts gives amorphous red-brown diamagnetic Ag(I)Ag(III)F(4), which transforms exothermally to brown, paramagnetic, microcrystalline Ag(II)F(2) below 0 degrees C. Ag(I)Au(III)F(4) prepared from Ag(+) and AuF(4)(-) in aHF has a tetragonal unit cell and a KBrF(4) type lattice, with a = 5.788(1) Å, c = 10.

Facile Routes to NiF(6)(2)(-), AgF(4)(-), AuF(6)(-), and PtF(6)(-) Salts Using O(2)(+) as a Source of O(2)F in Anhydrous HF.

O(2)(+) salts dissolved in liquid anhydrous hydrogen fluoride (aHF) at 20 degrees C or below oxidize aHF solutions of PtF(6)(2)(-) to PtF(6)(-). The parent base of O(2)(+) salts in aHF (O(2)F((solv))) generated with alkali fluoride is long-lived below -50 degrees C. An aHF solution of O(2)F((solv)) oxidizes Au(III) to Au(V) below -50 degrees C (2O(2)F((solv)) + AuF(4)(-)((solv)) --> AuF(6)(-)((solv)) +2O(2(g))).

Induction of hepatic 8-oxo-deoxyguanosine adducts by 2,3,7,8-tetrachlorodibenzo-p-dioxin in Sprague-Dawley rats is female-specific and estrogen-dependent.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a hepatocarcinogen that induces sex-specific hepatic neoplastic alterations in female, but not male, rats. It has been hypothesized that TCDD-induced alterations in estrogen metabolism lead to increased generation of reactive oxygen species. The resulting oxidative damage to DNA may contribute to TCDD-induced tumor promotion and hepatocarcinogenesis.

Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced tumor promotion by 17 beta-estradiol in female Sprague--Dawley rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in female but not in male rats. In an initiation-promotion model, ovariectomy inhibits TCDD-induced cell replication and reduces both TCDD-induced tumor formation and the promotion of enzyme-altered hepatocellular foci (AHF). The aim of this study was to determine the involvement of the ovarian hormone 17 beta-estradiol in the induction of cell proliferation and development of putative preneoplastic AHF following chronic exposure to TCDD.

Increased tumor necrosis factor-alpha production by peripheral blood leukocytes from TCDD-exposed rhesus monkeys.

Previous work has shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with a dose-dependent increase in the incidence and severity of endometriosis in the rhesus monkey. Studies also suggest that immune mechanisms participate in TCDD-mediated toxicity and the pathogenesis of endometriosis. Thirteen years after TCDD treatment was terminated, we characterized the phenotypic distribution of peripheral blood mononuclear cells (PBMC) from TCDD-exposed and -unexposed rhesus monkeys and determined the ability of these cells to produce cytokines and exert cytolytic activity against NK and T-cell-sensitive cell lines.

Gas-phase molecular structures of third row transition-metal hexafluorides WF6, ReF6, OsF6, IrF6, and PtF6. An electron-diffraction and ab initio study.

The molecular structures of WF6, ReF6, OsF6, IrF6, and PtF6 have been measured by electron diffraction from the gases, the last from both PtF6 itself and from a vapor assumed to consist of a mixture of O2 and PtF6 obtained by heating the salt O2PtF6. For models of Oh symmetry the bond lengths in the first three members of the series are essentially identical, but the Ir-F and Pt-F bonds are respectively about 0.01 and 0.

Serum levels of TCDD and dioxin-like chemicals in Rhesus monkeys chronically exposed to dioxin: correlation of increased serum PCB levels with endometriosis.

Humans and animals are exposed daily to a complex mixture of polyhalogenated aromatic hydrocarbons (PHAHs). Previous work has shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with a dose-dependent increase in the incidence and severity of endometriosis in the rhesus monkey. Dioxin-like chemicals can also exert effects in combination with TCDD via the aryl hydrocarbon receptor.

Induction of lung lesions in female rats following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8,-Tetrachlorodibenzo-p-dioxin (TCDD) has been classified as a known human carcinogen, and epidemiologic studies identify the lung as one of the target organs. Few experimental studies have attempted to characterize pulmonary effects of TCDD exposure. In this study, we characterize the induction of lesions in the lung by chronic oral TCDD exposure in diethylnitrosamine (DEN)-initiated or noninitiated female Sprague-Dawley rats.

Endotoxin (lipopolysaccharide)-induced nitric oxide production in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated Fischer rats: detection of nitrosyl hemoproteins by EPR spectroscopy.

Electron paramagnetic resonance (EPR) spectroscopy was used to study the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on endotoxin (lipopolysaccharide)-induced nitric oxide (NO) production in Fischer rats. We found that rats treated with 50 microg/kg TCDD had increased sensitivity to endotoxin, resulting in an approximately 2-fold increase in the level of NO production detected as nitrosylhemoglobin (HbNO) in venous blood. At lower concentrations (< or = 5 microg/kg), TCDD did not affect the endotoxin-induced NO production.

Levels of seven urinary phthalate metabolites in a human reference population.

Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate.

Ovarian tumors in rats induced by chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multispecies reproductive toxicant, and it has been recently classified by IARC as a known human carcinogen. Here, we report that TCDD promotes the development of ovarian tumors in an initiation-promotion model in female Sprague Dawley rats. Rats were initiated with diethylnitrosamine (DEN) or vehicle at 70 days of age.

Parting thoughts.

It has been said that there is no stronger urge than the urge to edit someone else's writing. Upon my retirement from the National Institute of Environmental Health Sciences (NIEHS), and concurrently from my position as co-editor-in-chief of Environmental Health Perspectives, I find that perhaps the stronger urge is not to edit but rather to editorialize. Therefore, I would like to provide some parting thoughts, and with them hopefully some insights gained from my experiences, which have spanned the broad spectrum of environmental health, from basic science to public health policy to science communication.

Toxicity of chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in diethylnitrosamine-initiated ovariectomized rats implanted with subcutaneous 17 beta-estradiol pellets.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in female but not in male rats. Several lines of evidence suggest a key role of ovarian hormones, presumably estrogen, in the mechanism of TCDD-induced hepatocarcinogenesis. The aim of this current study was to determine the toxicity of co-treatment with TCDD and 17 beta-estradiol and assess the efficacy of 90-day subcutaneous constant release 17 beta-estradiol pellets.

Hepatocarcinogenesis in female Sprague-Dawley rats following discontinuous treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In this study, we investigated the time course of promotion of tumors and putatively preneoplastic altered hepatic foci in the livers of diethylnitrosamine (DEN)-initiated female Sprague-Dawley rats. These rats had been treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) under different dosing regimens, but we used the same administered biweekly dose of 1.75 microg/kg of body weight.

Levels of methyleugenol in a subset of adults in the general U.S. population as determined by high resolution mass spectrometry.

We developed a sensitive and accurate analytical method for quantifying methyleugenol (ME) in human serum. Our method uses a simple solid-phase extraction followed by a highly specific analysis using isotope dilution gas chromatography-high resolution mass spectrometry. Our method is very accurate; its limit of detection is 3.

Strategies for assessing the implications of malformed frogs for environmental health.

The recent increase in the incidence of deformities among natural frog populations has raised concern about the state of the environment and the possible impact of unidentified causative agents on the health of wildlife and human populations. An open workshop on Strategies for Assessing the Implications of Malformed Frogs for Environmental Health was convened on 4-5 December 1997 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. The purpose of the workshop was to share information among a multidisciplinary group with scientific interest and responsibility for human and environmental health at the federal and state level.

Dose-dependent localization of TCDD in isolated centrilobular and periportal hepatocytes.

Dose-response relationships for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest a differential sensitivity of liver cell types to the induction of cytochrome P450 gene expression, and that the induction of hepatic protein CYP1A2 causes sequestration of TCDD. In addition, immunolocalization of hepatic CYP1A1/1B1/1A2 proteins is not uniform after exposure to TCDD. The mechanism for the regio-specific induction of hepatic P450s by TCDD is unknown, but may involve the differential distribution of participants in the AhR-mediated pathway and/or regional P450 isozymes, as well as, non-uniform distribution/sequestration of TCDD.