June 2016 - Issue 7
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.
Electronic cigarettes will soon face the same regulatory requirements as traditional cigarettes and smokeless tobacco products. E-cigarettes deliver nicotine to the respiratory tract without exposure to the more than 7,000 compounds (some of which are known to be toxic) produced by products that combust tobacco. But testing these emerging products will require new methods for conducting required inhalation exposure studies. Researchers at Battelle have been working for the last three years to perfect aerosolization methods and in vivo methodologies to help manufacturers meet the new requirements.
While some manufacturers have long conducted in vivo toxicology studies of cigarettes and other combustible and smokeless tobacco products, the Tobacco Control Act of 2009 established regulations requiring extensive characterization of regulated tobacco products before new products are marketed in the United States. The new FDA Deeming ruling, published in the Federal Register May 10, extends these requirements to e-cigarettes, hookahs, pipe tobacco, premium cigars, little cigars and other emerging tobacco products.
Unlike some tobacco products that burn tobacco to produce smoke, e-cigarettes heat liquids containing a vehicle, nicotine, flavorings and other chemicals to generate an inhalable aerosol. Complicating matters, there are dozens of different types of e-cigarettes on the market with different shapes, delivery systems, heating mechanisms and vehicle formulations. Each of these variables, along with variations in user behavior, may impact product performance.
Researchers began working on these challenges in 2013 as an internal research project in order to prepare for the eventual FDA regulation of e-cigarettes. This foundational research will allow Battelle to conduct well-controlled and characterized studies of e-cigarette products. Battelle is also working with manufacturers to optimize specialized aerosol generation equipment for future e-cigarette studies.
To better meet the needs of the industry, Battelle has recently doubled its lab space for inhalation toxicology studies. The Battelle Inhalation Toxicology Center is now among the largest specialized in vivo laboratories in the United States, with capacity to perform specialized inhalation studies to help manufacturers accelerate study timelines. In addition to standard study types, Battelle has the ability to work with a customer to design studies to address unique challenges. The Inhalation Toxicology Center brings together expertise in toxicology, pathology, biochemistry, engineering, aerosolization, and many other related fields in order to develop and validate new methods. In addition to tobacco studies, the Center performs extensive research for the National Toxicology Program and the pharmaceutical industry.
Battelle has been working at the forefront of tobacco and nicotine research since 1960 and has extensive experience conducting in vivo inhalation toxicology studies for traditional tobacco products, including cigarettes and other combustible products. In addition to extensive in vivotoxicology work, Battelle also provides product characterization as well as human exposure and behavioral studies through the Battelle Public Health Center for Tobacco Research. The e-cigarette research is a continuation of Battelle’s historical tobacco Harm Reduction efforts.
Battelle’s ongoing internal research will inform development of a knowledge database that will help the FDA and manufacturers better understand how all of the different variables in e-cigarette design and product formulation impact exposure risks.
Battelle has again been chosen to protect our warfighters and the general public against dangerous infectious disease and chemical threats under a new contract award. The research, which is funded by the U.S. Army Joint Program Executive Office, is part of an OASIS contract mechanism that is worth up to $59 million, including all options, over the next five years.
For decades, Battelle has conducted research designed to protect the military from these threats. Frequently, the vaccines and therapeutics developed and tested on these programs then make their way to protecting the civilian populace.
Work covered by this latest contract includes development of vaccines for potentially weaponized threats such as plague, botulinum, equine encephalitis, and filovirus, as well as medical countermeasures against multiple nerve agents and poisonous toxins used in chemical warfare.
“We’re proud of the work we do at Battelle to protect people from threats like the Ebola and Zika viruses and ricin,” said Julie Swick, general manager for Battelle’s Life Sciences Research group. “Our dedicated employees come into work every day knowing they are contributing solutions to important, worldwide problems.”
2-Deoxy-d-glucose (2-DG) is being developed as a potential anticonvulsant and disease-modifying agent for patients with epilepsy; however, during preclinical development, cardiac toxicity has been encountered in animal models. This study was performed to determine whether cardiac troponin (cTnI and cTnT), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and/or creatine kinase (CK) could be useful as indicators of 2-DG cardiac toxicity.
In addition, this study also investigated the association of cardiac histopathological changes with these biomarkers. F344 rats (4/sex/group/sacrifice point) were gavaged with either vehicle or 2-DG (50, 125, or 375 mg/kg twice daily; total daily dose of 100, 250, or 750 mg/kg/d) for 7, 14, 21, or 45 days followed by a 15-day recovery. Dose-dependent increases in NT-proBNP and BNP plasma concentrations were observed.
Following recovery period, the NT-proBNP and BNP concentrations returned to baseline levels. There were no remarkable increases in CK, ANP, cTnI, or cTnT concentrations. There were no gross cardiac lesions observed at the necropsy. Microscopic findings of vacuolar degeneration and hypertrophy of the endothelial cells of the endocardium were present in the heart at doses of 250 and 750 mg/kg/d. Microscopic findings, in general, were associated with increases in NT-proBNP levels. Cardiac toxicity appeared to be reversible. In conclusion, NT-proBNP and BNP are potential early biomarkers for 2-DG-induced cardiac toxicity that can be useful to monitor 2-DG therapy in clinical trials.
Download entire paper from the International Journal of Toxicology here.
Two scientists from the Battelle Life Science Research team have been nominated for the 2016 Charles C. Shepard Science Award. Nancy Niemuth, Statistician, and Dr. Carol Sabourin, Senior Research Leader and Chief Scientist, were nominated along with their collaborators for their paper Bridging non-human primate correlates of protection to reassess the Anthrax Vaccine Adsorbed booster schedule in humans.
Since 1985, the Centers for Disease Control and Prevention (CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR) have presented the Charles C. Shepard Science Award to authors of the most outstanding peer-reviewed research papers published by CDC/ATSDR scientists during the preceding year. The award recognizes scientific achievement at CDC/ATSDR and honors the memory of Dr. Charles C. Shepard, whose career was marked by the pursuit of scientific excellence. Presently, in addition to honoring publications in four categories – Assessment; Prevention and Control; Laboratory Science; and Data Methods and Study Design – there is also an award for Lifetime Scientific Achievement.
Nomination for the Shepard Science Award is given in recognition of special contribution to the mission of CDC/ATSDR and to public health. The winners for the different categories will be revealed at a ceremony on June 8 on the CDC Roybal Campus at the Centers for Disease Control and Prevention.
Congratulations to Nancy, Carol and their colleagues from the CDC.
Read the full paper here:
Bridging non-human primate correlates of protection to reassess the Anthrax Vaccine Adsorbed booster schedule in humans
by Jarad M. Schiffer, Ligong Chen, Shannon Dalton, Nancy A. Niemuth, Carol L. Sabourin, and Conrad P. Quinn
Chemical warfare agents and other toxins present tremendous dangers for military personnel working in war zones. Dr. Jill Harvilchuck is working to bring new medical countermeasures to market to better protect soldiers and civilians.
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