Calibration and validation of toxicokinetic-toxicodynamic models for three neonicotinoids and some aquatic macroinvertebrates

Ecotoxicology - Exposure patterns in ecotoxicological experiments often do not match the exposure profiles for which a risk assessment needs to be performed. This limitation can be overcome by...     

Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 2. Ecotoxicology

Gas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a catalytic process known as the Fischer–Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons which can subsequently be refined to a range of products analogous to those obtained from petroleum refining. However, in contrast to their petroleum-derived analogs, GTL products are essentially free of unsaturated or aromatic compounds and do not contain any sulfur-, oxygen-, or nitrogen-containing compounds. Under new chemical substance notification requirements, an extensive testing program covering the entire portfolio of GTL products has been undertaken to assess their hazardous properties to human health and environment. The results of these studies have been summarized in a two-part review. Part 1 provides an overview of the mammalian toxicity hazardous properties of the various GTL products. This second part of the review focuses on the aquatic, sediment, terrestrial, and avian toxicity studies which assess the ecotoxicological hazard profile of the GTL products. Many challenges were encountered during these tests relating to dosing, analysis and interpretation of results. These are discussed with the intent to share experiences to help inform and shape future regulatory mandates for testing of poorly soluble complex substances. As was the case with the mammalian toxicology review, there were a few cases where adverse effects were found, but overall the GTL products were found to exert minimal adverse ecotoxicological effects and these were less severe than effects observed with their conventional, petroleum-derived analogs.     

Definitions and statistical properties of master protocols for personalized medicine in oncology

ABSTRACT

Within the field of cancer research, discovery of biomarkers and genetic mutations that are potentially predictive of treatment benefit is motivating a paradigm shift in how cancer clinical trials are conducted. In this review, we provide an overview of the class of trials known as “master protocols,” including basket trials, umbrella trials, and platform trials. For each, we describe standardized terminology, provide a motivating example with modeling details and decision rules, and discuss statistical advantages and limitations. We conclude with a discussion of general statistical considerations and challenges encountered across these types of trials.     

Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals

Pharmaceuticals are ubiquitous in the natural environment with concentrations expected to rise as human population increases. Environmental risk assessments are available for a small portion of pharmaceuticals in use, raising concerns over the potential risks posed by other drugs that have little or no data. With >1900 active pharmaceutical ingredients in use, it would be a major task to test all of the compounds with little or no data. Desk-based prioritization studies provide a potential solution by identifying those substances that are likely to pose the greatest risk to the environment and which, therefore, need to be considered a priority for further study. The aim of this review was to (1) provide an overview of different prioritization exercises performed for pharmaceuticals in the environment and the results obtained; and (2) propose a new holistic risk-based prioritization framework for drugs in the environment. The suggested models to underpin this framework are discussed in terms of validity and applicability. The availability of data required to run the models was assessed and data gaps identified. The implementation of this framework may harmonize pharmaceutical prioritization efforts and ensure that, in the future, experimental resources are focused on molecules, endpoints, and environmental compartments that are biologically relevant.