Which prenatal biomarker is most appropriate for methylmercury dose-response for neurodevelopmental effects?

Developmental neurotoxicity (DNT) is a well-established hazard attributed to methylmercury (MeHg) exposure. This evidence is based primarily upon includes studies that measured biomarkers of MeHg exposure in samples of maternal hair and blood, and cord blood. The aim of this review was to investigate which of these prenatal biomarkers is most appropriate for quantifying the DNT effects attributed to MeHg.

Total Blood Mercury Predicts Methylmercury Exposure in Fish and Shellfish Consumers.

Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure sources and toxicological effects than MeHg. Therefore, estimating the whole blood MeHg/THg ratio is critical to predicting MeHg exposure and, subsequently, efforts to establish an exposure-response relationship for use in risk assessment.

Seafood, wine, rice, vegetables, and other food items associated with mercury biomarkers among seafood and non-seafood consumers: NHANES 2011-2012.

Fish/seafood consumption is a source of mercury; other dietary sources are not well described. This cross-sectional study used National Health and Nutrition Examination Survey (NHANES) 2011-2012 data. Participants self-reported consuming fish/seafood (N = 5427) or not (N = 1770) within the past 30 days.

A systematic review of the association between pleural plaques and changes in lung function.

Objectives: To conduct a systematic review of changes in lung function in relation to presence of pleural plaques in asbestos-exposed populations.

Methods: Database searches of PubMed and Web of Science were supplemented by review of papers' reference lists and journals' tables of contents. Methodological features (eg, consideration of potential confounding by smoking) of identified articles were reviewed by ≥ two reviewers.

Human health effects of tetrachloroethylene: key findings and scientific issues.

Background: The U.S. Environmental Protection Agency (EPA) completed a toxicological review of tetrachloroethylene (perchloroethylene, PCE) in February 2012 in support of the Integrated Risk Information System (IRIS).

Influence of exposure assessment and parameterization on exposure response. Aspects of epidemiologic cohort analysis using the Libby Amphibole asbestos worker cohort.

Recent meta-analyses of occupational epidemiology studies identified two important exposure data quality factors in predicting summary effect measures for asbestos-associated lung cancer mortality risk: sufficiency of job history data and percent coverage of work history by measured exposures. The objective was to evaluate different exposure parameterizations suggested in the asbestos literature using the Libby, MT asbestos worker cohort and to evaluate influences of exposure measurement error caused by historically estimated exposure data on lung cancer risks. Focusing on workers hired after 1959, when job histories were well-known and occupational exposures were predominantly based on measured exposures (85% coverage), we found that cumulative exposure alone, and with allowance of exponential decay, fit lung cancer mortality data similarly.

Low levels of exposure to libby amphibole asbestos and localized pleural thickening.

Objective: To explore the relationship between low levels of exposure to Libby amphibole asbestos (LAA) and pleural abnormalities, specifically localized pleural thickening (LPT).

Methods: Three studies presenting the risks associated with quantitative LAA exposure estimates were reviewed, paying particular attention to lower exposure ranges.

Results: Studies reviewed were conducted among workers exposed to LAA at mining and milling operations in Libby, Montana, at a vermiculite processing facility in Marysville, Ohio, and community residents exposed to LAA from a vermiculite processing facility in Minneapolis, Minnesota.

Nonparametric Bayesian methods for benchmark dose estimation.

The article proposes and investigates the performance of two Bayesian nonparametric estimation procedures in the context of benchmark dose estimation in toxicological animal experiments. The methodology is illustrated using several existing animal dose-response data sets and is compared with traditional parametric methods available in standard benchmark dose estimation software (BMDS), as well as with a published model-averaging approach and a frequentist nonparametric approach. These comparisons together with simulation studies suggest that the nonparametric methods provide a lot of flexibility in terms of model fit and can be a very useful tool in benchmark dose estimation studies, especially when standard parametric models fail to fit to the data adequately.

Localized pleural thickening: smoking and exposure to Libby vermiculite.

There is limited research on the combined effects of smoking and asbestos exposure on risk of localized pleural thickening (LPT). This analysis uses data from the Marysville cohort of workers occupationally exposed to Libby amphibole asbestos (LAA). Workers were interviewed to obtain work and health history, including ever/never smoking and chest X-rays.

Physiologically based pharmacokinetic model use in risk assessment--Why being published is not enough.

A panel of experts in physiologically based pharmacokinetic (PBPK) modeling and relevant quantitative methods was convened to describe and discuss model evaluation criteria, issues, and choices that arise in model application and computational tools for improving model quality for use in human health risk assessments (HHRAs). Although publication of a PBPK model in a peer-reviewed journal is a mark of good science, subsequent evaluation of published models and the supporting computer code is necessary for their consideration for use in HHRAs. Standardized model evaluation criteria and a thorough and efficient review process can reduce the number of review and revision iterations and hence the time needed to prepare a model for application.

Approaches to cancer assessment in EPA's Integrated Risk Information System.

The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) Program develops assessments of health effects that may result from chronic exposure to chemicals in the environment.

Parameters of a dose-response model are on the boundary: what happens with BMDL?

It is well known that, under appropriate regularity conditions, the asymptotic distribution for the likelihood ratio statistic is chi(2). This result is used in EPA's benchmark dose software to obtain a lower confidence bound (BMDL) for the benchmark dose (BMD) by the profile likelihood method. Recently, based on work by Self and Liang, it has been demonstrated that the asymptotic distribution of the likelihood ratio remains the same if some of the regularity conditions are violated, that is, when true values of some nuisance parameters are on the boundary.

Towards quantitative uncertainty assessment for cancer risks: central estimates and probability distributions of risk in dose-response modeling.

Regulatory agencies and the scientific community have been engaged in a long-term effort to strengthen health risk assessment procedures. Recently the momentum of this effort has accelerated to increasing biological information for a variety of toxic compounds and emphasis on the policy goal of broader characterization of scientific uncertainty (in contrast to providing only a single risk estimate). For example, the OMB Regulatory Analysis Guidelines [OMB, 2003.

Intraoperative infrared imaging of brain tumors.

Object: Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear.

Methods: An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis-astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy.

Enhancing encoding of a motor memory in the primary motor cortex by cortical stimulation.

Motor training results in encoding of motor memories, a form of use-dependent plasticity. Here we tested the hypothesis that transcranial magnetic stimulation (TMS) synchronously applied to a motor cortex engaged in a motor training task could enhance this plastic process. Healthy volunteers were studied in four sessions: training consisting of performance of directionally specific voluntary thumb movements (Train alone), training with TMS delivered during the execution of the training movement in a strictly temporal relationship to the motor cortex contralateral (Train+TMS synchronous(contra)) and ipsilateral (Train+TMS synchronous(ipsi)) to the training hand, and training with TMS delivered asynchronous to the training movement to the motor cortex contralateral to the training hand (Train+TMS asynchronous(contra)).

Age-dependent changes in the ability to encode a novel elementary motor memory.

In healthy individuals, motor training elicits cortical plasticity that encodes the kinematic details of the practiced movements and is thought to underlie recovery of function after stroke. The influence of age on this form of plasticity is incompletely understood. We studied 55 healthy subjects and identified a substantial decrease in training-dependent plasticity as a function of age in the absence of differences in training kinematics.

Modulation of use-dependent plasticity by d-amphetamine.

Use-dependent plasticity, thought to contribute to functional recovery after brain injury, is elicited by motor training. The purpose of this study was to determine if administration of d-amphetamine facilitates the effects of motor training on use-dependent plasticity. Healthy human volunteers underwent a training period of voluntary thumb movements under the effects of placebo or d-amphetamine in different sessions in a randomized double-blind, counterbalanced design.