Developmental dental aberrations after the dioxin accident in Seveso.

Children's developing teeth may be sensitive to environmental dioxins, and in animal studies developing teeth are one of the most sensitive targets of toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Twenty-five years after the dioxin accident in Seveso, Italy, 48 subjects from the contaminated areas (zones A and B) and in patches lightly contaminated (zone R) were recruited for the examination of dental and oral aberrations. Subjects were randomly invited from those exposed in their childhood and for whom frozen serum samples were available.

Serum dioxin concentrations and age at menarche.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is associated with delays in pubertal development in animal studies. On 10 July 1976, as a result of a chemical explosion, residents of Seveso, Italy, experienced the highest levels of TCDD exposure experienced by a human population. Twenty years later, we initiated the Seveso Women's Health Study (SWHS), a retrospective cohort study of female residents of the most contaminated areas, to determine whether the women were at higher risk for reproductive disease.

Comparison of 1-hydroxypyrene exposure in the US population with that in occupational exposure studies.

Urine samples collected in 1999 and 2000 as part of the National Health and Nutrition Examination Survey (NHANES) were analyzed for 14 monohydroxy polycyclic aromatic hydrocarbons (PAHs), and, for the first time, reference range values were calculated for these metabolites in the US population. Pyrene is a major component of most PAH mixtures and often is used as a surrogate for total PAH exposure. We detected 1-hydroxypyrene (1-OHpyrene), a metabolite of pyrene, in more than 99% of the samples.

In utero exposure to polychlorinated biphenyls and sensorineural hearing loss in 8-year-old children.

Early-life exposure to polychlorinated biphenyls (PCBs), a ubiquitous environmental contaminant, increases the hearing threshold at selected frequencies in rats. Among humans from the Faroe Islands with unusually high early-life PCB exposure, exposure was directly associated with increased hearing thresholds at two frequencies, although the deficits were present in the left ear but not the right. We examined PCB levels in maternal pregnancy serum in relation with audiometrically determined hearing thresholds among offspring when they were of school age.

Automated solid-phase extraction and measurement of perfluorinated organic acids and amides in human serum and milk.

Organic fluorochemicals are used in multiple commercial applications including surfactants, lubricants, paints, polishes, food packaging, and fire-retarding foams. Recent scientific findings suggest that several perfluorochemicals (PFCs), a group of organic fluorochemicals, are ubiquitous contaminants in humans and animals world wide. Furthermore, concern has increased about the toxicity of these compounds.

Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State.

A total organophosphorus pesticide exposure study was conducted in Washington State in 1998 in a sample population of 13 children aged 2.5-5.5 years.

Measurement of dialkyl phosphate metabolites of organophosphorus pesticides in human urine using lyophilization with gas chromatography-tandem mass spectrometry and isotope dilution quantification.

Urinary dialkylphosphate (DAP) metabolites have been used to estimate human exposure to organophosphorus pesticides. We developed a method for quantifying the six DAP urinary metabolites of at least 28 organophosphorus pesticides using lyophilization and chemical derivatization followed by analysis using isotope-dilution gas chromatography-tandem mass spectrometry (GC-MS/MS). Urine samples were spiked with stable isotope analogues of the DAPs and the water was removed from the samples using a lyophilizer.

Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit.

Objective: Premature neonates who spend time in a neonatal intensive care unit may be at increased risk of adverse health effects from exposure to di-(2-ethylhexyl) phthalate (DEHP) because of their increased risk of high exposure, their small body size, and their physical condition. DEHP, a reproductive toxicant in animals, is a major component in polyvinyl chloride (PVC) plastics, which are frequently used in medical tubing and blood storage bags. DEHP is not covalently bound to PVC, and it may be easily released from the PVC medical devices.

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.

Retrospective time-trend study of polybrominated diphenyl ether and polybrominated and polychlorinated biphenyl levels in human serum from the United States.

Six polybrominated diphenyl ethers (PBDEs), one hexabromobiphenyl [polybrominated biphenyl (PBB)], and one hexachlorobiphenyl [polychlorinated biphenyl (PCB)] were measured in 40 human serum pools collected in the southeastern United States during 1985 through 2002 and in Seattle, Washington, for 1999 through 2002. The concentrations of most of the PBDEs, which are commercially used as flame retardants in common household and commercial applications, had significant positive correlations with time of sample collection, showing that the concentrations of these compounds are increasing in serum collected in the United States. In contrast, PCB and PBB levels were negatively correlated with sample collection year, indicating that the levels of these compounds have been decreasing since their phaseout in the 1970s.

Analysis of human urine for fifteen phthalate metabolites using automated solid-phase extraction.

We improved our previous analytical method to measure phthalate metabolites in urine as biomarkers for phthalate exposure by automating the solid-phase extraction (SPE) procedure and expanding the analytical capability to quantify four additional metabolites: phthalic acid, mono-3-carboxypropyl phthalate, mono-isobutyl phthalate (miBP), and monomethyl isophthalate. The method, which involves automated SPE followed by isotope dilution-high performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS), allows for the quantitative measurement of 15 phthalate metabolites in urine with detection limits in the low ng/ml range. SPE automation allowed for the unattended sequential extraction of up to 100 samples at a time, and resulted in an increased sample throughput, lower solvent use, and better reproducibility than the manual SPE.

Automated solid phase extraction and quantitative analysis of human milk for 13 phthalate metabolites.

While the demonstrated benefits associated with breastfeeding are well recognized, breast milk is one possible route of exposure to environmental chemicals, including phthalates, by breastfeeding infants. Because of the potential health impact of phthalates to nursing children, determining whether phthalates are present in breast milk is important. We developed a sensitive method for measuring 13 phthalate metabolites in breast milk using automated solid phase extraction (SPE) coupled to isotope dilution-high-performance liquid chromatography (HPLC)-negative ion electrospray ionization-tandem mass spectrometry.

Aryl-hydrocarbon receptor-dependent pathway and toxic effects of TCDD in humans: a population-based study in Seveso, Italy.

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 upon immune and mechanistically based biomarkers of dioxin response in humans. TCDD toxic effects are known to be mediated by the aryl-hydrocarbon receptor (AhR). We randomly selected 62 study subjects from the highest exposed zones and 59 from the surrounding non-contaminated area.

Concentration-dependent TCDD elimination kinetics in humans: toxicokinetic modeling for moderately to highly exposed adults from Seveso, Italy, and Vienna, Austria, and impact on dose estimates for the NIOSH cohort.

Serial measurements of serum lipid 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 36 adults from Seveso, Italy, and three patients from Vienna, Austria, with initial serum lipid TCDD concentrations ranging from 130 to 144,000 ppt, were modeled using a modified version of a previously published toxicokinetic model for the distribution and elimination of dioxins. The original model structure accounted for a concentration-dependent increase in overall elimination rate for TCDD due to nonlinear distribution of TCDD to the liver (secondary to induction of the binding protein CYP1A2), from which elimination takes place via a first-order process. The original model structure was modified to include elimination due to lipid partitioning of TCDD from circulation into the large intestine, based on published human data.

Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.

We measured the urinary monoester metabolites of seven commonly used phthalates in approximately 2,540 samples collected from participants of the National Health and Nutrition Examination Survey (NHANES), 1999-2000, who were greater than or equal to 6 years of age. We found detectable levels of metabolites monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP) in > 75% of the samples, suggesting widespread exposure in the United States to diethyl phthalate, dibutyl phthalate or diisobutylphthalate, benzylbutyl phthalate, and di-(2-ethylhexyl) phthalate, respectively. We infrequently detected monoisononyl phthalate, mono-cyclohexyl phthalate, and mono-n-octyl phthalate, suggesting that human exposures to di-isononyl phthalate, dioctylphthalate, and dicyclohexyl phthalate, respectively, are lower than those listed above, or the pathways, routes of exposure, or pharmacokinetic factors such as absorption, distribution, metabolism, and elimination are different.

Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate.

Exposure to di-(2-ethylhexyl) phthalate (DEHP) is prevalent based on the measurement of its hydrolytic metabolite mono-(2-ethylhexyl) phthalate (MEHP) in the urine of 78% of the general U.S. population studied in the 1999-2000 National Health and Nutrition Examination Survey (NHANES).

Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population.

We report population-based concentrations, stratified by age, sex, and racial/ethnic groups, of dialkyl phosphate (DAP) metabolites of multiple organophosphorus pesticides. We measured dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP) concentrations in 1,949 urine samples collected in U.S.

APOE genotype-specific differences in human and mouse macrophage nitric oxide production.

Individuals expressing an APOE4 genotype demonstrate increased Alzheimer's disease (AD) neuropathology and a decreased onset age. The APOE4 gene may act by modulating the CNS immune response. Using human monocyte-derived macrophages (MDM), we show a significantly greater increase in NO production during immune activation in MDM from APOE4 AD patients compared to normal, age-matched individuals or to AD patients with an APOE 3/3 genotype.

Relationship of serum TCDD concentrations and age at exposure of female residents of Seveso, Italy.

In 1976, a chemical plant explosion near Seveso, Italy, resulted in the highest known exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in residential populations. In 1996, we initiated the Seveso Women's Health Study (SWHS), a historical cohort study of females who were 40 years old at the time of explosion and residents of the most heavily contaminated areas, zones A and B. Serum samples collected near the time of the explosion were analyzed for TCDD.

Simultaneous measurement of urinary bisphenol A and alkylphenols by automated solid-phase extractive derivatization gas chromatography/mass spectrometry.

Bisphenol A (BPA) and alkylphenols (APs) are widely used industrial chemicals. BPA is used to manufacture polycarbonate plastic and epoxy resins; APs are used to make alkylphenol ethoxylates, common nonionic surfactants. BPA and APs can leach into the environment during industrial production and after degradation of the polycarbonate plastics and nonionic surfactants.

Persistent organochlorines in the serum of the non-occupationally exposed New Zealand population.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and organochlorine pesticides were measured in the serum of a sample of the New Zealand population aged 15 years and older. This was the first study to obtain representative measures of PCDDs, PCDFs and PCBs in the adult population of an entire country. Serum samples were obtained in 1996-1997.

Glucuronidation patterns of common urinary and serum monoester phthalate metabolites.

Metabolism of most diesters of phthalic acid in humans occurs by an initial phase I biotransformation in which phthalate monoesters are formed, followed by a phase II biotransformation in which phthalate monoesters react with glucuronic acid to form their respective glucuronide conjugates. The phase II conjugation increases water solubility and facilitates urinary excretion of phthalate, and reduces the potential biological activity because the putative biologically active species is the monoester metabolite. In this study, we report percentages of glucuronidation of four common phthalate monoesters, monoethyl (mEP), monobutyl (mBP), monobenzyl (mBzP), and mono-2-ethylhexyl phthalate (mEHP) in a subset of urine (mEP n=262, mBP n=283, mBzP n=328, mEHP n=119) and serum (mEP n=93, mBP n=149, mEHP n=141) samples from the general US population.

Exposure assessment for endocrine disruptors: some considerations in the design of studies.

In studies designed to evaluate exposure-response relationships in children's development from conception through puberty, multiple factors that affect the generation of meaningful exposure metrics must be considered. These factors include multiple routes of exposure; the timing, frequency, and duration of exposure; need for qualitative and quantitative data; sample collection and storage protocols; and the selection and documentation of analytic methods. The methods for exposure data collection and analysis must be sufficiently robust to accommodate the a priori hypotheses to be tested, as well as hypotheses generated from the data.

Carryover effects of free reinforcement on children's work completion.

Patterns of behavior that persist during transition to a new set of contingencies are referred to as reinforcement history or carryover effects. The authors examined the carryover effects of a fixed-time (FT) schedule of free reinforcement on children's work completion and accuracy. Two female students with learning disabilities participated.