Concentration of metals in blood of Maine children 1-6 years old.

Blood lead concentrations are higher in young children than in other age groups, whereas little is known regarding concentrations of other metals in young children. We measured the concentrations of a suite of metals in the blood of children 1-6 years of age, and assessed potential differences by age, season, or region of Maine. We used blood submitted to the Maine State Health and Environmental Testing Laboratory for blood lead analysis to determine the concentrations of arsenic (As), antimony (Sb), cadmium (Cd), manganese (Mn), mercury (Hg), selenium (Se), tin (Sn), and uranium (U) in 1350 children 1-6 years of age.

Behavioral toxicology in the 21st century: challenges and opportunities for behavioral scientists. Summary of a symposium presented at the annual meeting of the neurobehavioral teratology society, June, 2009.

The National Research Council (NRC) of the National Academies of Science recently published a report of its vision of toxicity testing in the 21st century. The report proposes that the current toxicity testing paradigm that depends upon whole-animal tests be replaced with a strategy based upon in vitro tests, in silico models and evaluations of toxicity at the human population level. These goals are intended to set in motion changes that will transform risk assessment into a process in which adverse effects on public health are predicted by quantitative structure-activity relationship (QSAR) models and data from suites of high-throughput in vitro tests.

Behavioral changes in aging but not young mice after neonatal exposure to the polybrominated flame retardant decaBDE.

Background: After several decades of commercial use, the flame-retardant chemicals polybrominated diphenyl ethers (PBDEs) and their metabolites are pervasive environmental contaminants and are detected in the human body. Decabrominated diphenyl ether (decaBDE) is currently the only PBDE in production in the United States.

Objectives: Little is known about the health effects of decaBDE.

Does rapid metabolism ensure negligible risk from bisphenol A?

Background: Bisphenol A (BPA) risks are being evaluated by many regulatory bodies because exposure is widespread and the potential exists for toxicity at low doses.

Objective: We evaluated evidence that BPA is cleared more rapidly in humans than in rats in relation to BPA risk assessment.

Discussion: The European Food Safety Authority (EFSA) relied on pharmacokinetic evidence to conclude that rodent toxicity data are not directly relevant to human risk assessment.

Thyroid-disrupting chemicals: interpreting upstream biomarkers of adverse outcomes.

Background: There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health.

Objectives: We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals.

Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys and mice.

Alzheimer's disease (AD) is characterized by plaques of amyloid-beta (Abeta) peptide, cleaved from amyloid-beta protein precursor (AbetaPP). Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates.

The RegEx trial: a randomized, double-blind, placebo- and active-controlled pilot study combining regadenoson, a selective A(2A) adenosine agonist, with low-level exercise, in patients undergoing myocardial perfusion imaging.

Background: Although vasodilator stress myocardial perfusion imaging (MPI) is increasingly performed with exercise, adenosine A(2A) receptor agonists have not been studied with exercise.

Objectives: To determine the safety of administering regadenoson during exercise and, secondarily, to evaluate image quality, patient acceptance, and detection of perfusion defects.

Methods: Patients requiring pharmacologic MPI received a standard adenosine-supine protocol (AdenoSup, n = 60) and were then randomized (2:1) in a double-blind manner to low-level exercise with bolus intravenous injection of regadenoson (RegEx, n = 39) or placebo (PlcEx, n = 21).

Meeting report: moving upstream-evaluating adverse upstream end points for improved risk assessment and decision-making.

Background: Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an "adverse effect" in the context of hazard identification and risk assessment.

Overview of modifiers of methylmercury neurotoxicity: chemicals, nutrients, and the social environment.

It has been known for decades that methylmercury is a potent neurotoxicant, and that the developing brain is more susceptible to impairment as a result of methylmercury exposure than is the adult. Exposure to methylmercury is exclusively through consumption of fish and marine mammals. In recent years, the potential for protection against methylmercury toxicity by nutrients present in fish, particularly omega-3 fatty acids and selenium, has been explored in both epidemiological and experimental studies.

Risk factors for the perpetration of child sexual abuse: a review and meta-analysis.

Objectives: Since the late 1980s, there has been a strong theoretical focus on psychological and social influences of perpetration of child sexual abuse. This paper presents the results of a review and meta-analysis of studies examining risk factors for perpetration of child sexual abuse published since 1990.

Method: Eighty-nine studies published between 1990 and April of 2003 were reviewed.

Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial (RegCOPD trial).

Background: Patients with reactive airways are at risk for adenosine-induced bronchoconstriction, mediated via A(2B) and/or A(3) adenosine receptors.

Methods And Results: In this randomized, double-blind, placebo-controlled crossover trial, we examined the safety of regadenoson, a selective adenosine A(2A) receptor agonist, in patients with moderate chronic obstructive pulmonary disease (COPD) (n = 38) and patients with severe COPD (n = 11) with a baseline mean forced expiratory volume in 1 second (FEV(1)) of 1.74 +/- 0.

The new tapestry of risk assessment.

Neurotoxicology is entering a new phase in how it views and practices risk assessment. Perhaps more than any of the other disciplines that comprise the science of toxicology, it has been compelled to consider a daunting array of factors other than those directly coupled to chemical and dose, and the age and sex of the subject population. In epidemiological investigations, researchers are increasingly cognizant of the problems introduced by allegedly controlling for variables classified as confounders or covariates.

Co-localization and distribution of cerebral APP and SP1 and its relationship to amyloidogenesis.

Alzheimer's disease is characterized by amyloid-beta peptide (Abeta)-loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor (APP) and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 (SP1), which has been shown to be required for the regulation of APP and Abeta.

Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD.

The sporadic nature of Alzheimer's disease (AD) argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead (Pb) during brain development predetermined the expression and regulation of the amyloid precursor protein (APP) and its amyloidogenic beta-amyloid (Abeta) product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 (beta-site APP cleaving enzyme 1)] as well as their transcriptional regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as infants.

Developmental delays and locomotor activity in the C57BL6/J mouse following neonatal exposure to the fully-brominated PBDE, decabromodiphenyl ether.

After several decades of commercial use, the flame retardant chemicals polybrominated diphenyl ethers (PBDEs) and their metabolites have become pervasive environmental contaminants with a global distribution. PBDEs have entered the food chain and increasing levels can be detected in the human body. Decabrominated diphenyl ether (decaBDE) is currently the most widely used of the PBDEs in the United States.

Evaluation of the U.S. EPA/OSWER preliminary remediation goal for perchlorate in groundwater: focus on exposure to nursing infants.

Background: Perchlorate is a common contaminant of drinking water and food. It competes with iodide for uptake into the thyroid, thus interfering with thyroid hormone production. The U.

The presence of AC133-positive cells suggests a possible role of endothelial progenitor cells in the formation of choroidal neovascularization.

Purpose: Recent evidence suggests that vasculogenesis as well as angiogenesis occurs throughout the body during neovascularization. The recruitment of circulating stem cells is a key feature of vasculogenesis. The purpose of the present study was to determine whether markers of endothelial progenitor cells (EPCs) are present in choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Prenatal methylmercury exposure affects spatial vision in adult monkeys.

Decades of research have demonstrated that exposure to methylmercury (MeHg), a ubiquitous environmental pollutant, can have both early and long-term neurobehavioral consequences in exposed offspring. The present study assessed visual functioning in adult macaque monkeys (Macaca fascicularis) exposed in utero to 0, 50, 70, or 90 microg/kg/day of MeHg hydroxide. Twenty-one full-term, normal birth weight offspring (9 controls, 12 exposed) were tested at approximately 11-14.

The NAS perchlorate review: questions remain about the perchlorate RfD.

Human exposure to perchlorate is commonplace because it is a contaminant of drinking water, certain foods, and breast milk. The U.S.

Assessing the effects of environmental toxicant exposure in developmental epidemiological studies: issues for risk assessment.

Epidemiological studies have been of critical importance to the understanding of the effects of environmental chemical exposure during development on the behavior of infants and children. The ultimate goal of these studies should be to provide information that may be used directly for the protection of public health. The strategies for the assessment endpoints include development of domain-specific tests based on knowledge concerning effects of the chemicals being assessed, or use of standard clinical instruments that sample a range of functions.

The US EPA reference dose for methylmercury: sources of uncertainty.

The US Environmental Protection Agency (EPA) derived a reference dose for methylmercury in 2001, based on an extensive analysis by the National Research Council (NRC) of the National Academy of Sciences. The NRC performed benchmark dose analysis on a number of endpoints from three longitudinal prospective studies: the Seychelles Islands, the Faroe Islands, and the New Zealand studies. Adverse effects were reported in the latter two studies, but not in the Seychelles study.