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October 2016 - Issue 9
Welcome to Battelle’s Life Sciences Research CRO+ Today Newsletter. The Battelle Life Sciences Research team provides fast, accurate answers for discovery, safety and efficacy with our integrated scientific and technological capabilities, world-class facilities and ability to meet technical, development and regulatory needs. Battelle Life Sciences CRO+ Today will keep you up-to-date on cutting-edge life sciences research.
Both cardiovascular (CV) and neurobehavioral testing are needed for Safety Pharmacology evaluations. However, it can be time and cost intensive to conduct a full battery of CV and central nervous system (CNS) tests. One promising solution is to conduct CV and CNS testing simultaneously. A recent Battelle study demonstrates that simultaneous testing produces CV data comparable to data collected during stand-alone CV tests, with the added benefit of also capturing CV changes while animals are actively performing their neurobehavioral tasks.
Simultaneous testing provides significant advantages for safety pharmacology and chemical safety testing. Performing both sets of tests together reduces timelines and costs for companies. It also reduces the number of animals needed to conduct testing, minimizes stress on the animals and allows CV measurement while under baseline conditions, while actively performing in forced or spontaneous activity tests, and under reflex tests.
Using simultaneous testing techniques, researchers can look at changes in telemetric readings and task performance with the same animal under exposed and non-exposed conditions, so that each subject acts as its own control. Taking simultaneous readings also allows researchers to better understand how CV and CNS effects are interrelated. For example, there is a large increase in heart rate seen when animals are performing on the Rotarod that quickly returns to baseline when animals are in their inter-trial interval period. The CV and behavioral profile show similar increases in heart rate and performance with drugs like amphetamine but are discordant with drugs like MK-801, which increases heart rate dramatically but significantly impairs performance.
Battelle researchers are optimizing techniques for simultaneous CV and CNS testing. In part, this involves technical considerations, such as placement of telemetry equipment so that it does not interfere with task performance. Measurement issues, such as the different time intervals for data collection of CV vs. CNS data, also present challenges for simultaneous testing. Battelle researchers have developed data collection and analysis methods to enable close temporal matching of CNS and CV effects.
In the Battelle study, rats instrumented with telemetry transmitters were assessed in a series of CNS tests, including acoustic startle response, motor activity and Rotarod. Measurements for both CV and CNS responses were made under baseline conditions and while subjects were exposed to three drugs with well-understood CV and CNS effects. The results demonstrated accurate simultaneous detection of changes in CV and CNS data during performance of neurobehavioral tasks. Cardiovascular endpoints were impacted by performance in these tasks and by drug challenge.
Battelle researchers are continuing to refine methods for simultaneous CV and CNS testing. These methods will help the pharmaceutical industries streamline studies while providing clear, accurate data needed to understand the CV and neurological effects of their products.
Phorate is an extremely toxic broad-use insecticide and ascaricide, commonly applied as a granular agricultural product for long-term release and systemic uptake by plants to control specific pests, such as sucking insects on peanut and nematodes in soybean plants. Battelle researchers conducted a study to characterize the oral toxicity of phorate oxon (PHO), with an emphasis on gender- and age-related effects.
Agricultural use of phorate has been linked to adverse environmental consequences and identified as a potential public health concern. Phorate is rapidly metabolized by plants, insects and mammals into several organophosphorus (OP) anti-cholinesterase (anti-ChE) intermediates that are even more toxic than the parent compound. While animal toxicity data of the parent compound phorate has been reported, relatively little is known about its more toxic metabolites. Battelle researchers recently published the results of a study that 1) evaluated the oral/ingestion toxicity of PHO in the Sprague-Dawley rat and 2) investigated and characterized any potential differences in susceptibility due to gender and age.
The study was coauthored by Battelle researchers Michael Babin, Kevin G. McGarry and Thomas H. Snider, along with David A. Jett, Gennady E. Platoff Jr. and David T. Yeung of the National Institutes of Health (NIH).
Dr. Michael Babin is working to keep soldiers and civilians safe from chemical threats. A Toxicologist at the Battelle Biomedical Research Center (BBRC), he designs and runs studies to evaluate medical countermeasures against toxic chemicals and chemical weapons.
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