Toxicology Studies

 


Acute and Repeat Dose
Toxicology studies are a mandatory requirement in the drug development process and are conducted to characterize the structural (physical / pathology related) effects of a test article following a single or repeated administration. Such studies are intended to identify target organs, exposure / response relationships, and potential reversibility of toxic effects. This information is required as part of the safety assessment supporting the conduct of human clinical trials.

Drug Development Timeline

Recent Advancements 
Many researchers have chosen to include 24-hour continuous monitoring and assessment of functional effects in repeat dose toxicology studies as a means of providing an improved risk assessment. The functional endpoints most commonly included are those typically collected as part of the core battery of Safety Pharmacology studies (ICH S7AS7B); especially the cardiovascular endpoints available from ECG and blood pressure measurements.

Additional advantages of including 24-hour continuous monitoring include: 
  • The ability to collect data from conscious, free roaming animals that are not confounded by anesthesia or response to human factors, more closely representing the clinical situation
  • Monitoring of both structural and functional endpoints in the same study by combining Safety Pharmacology and Toxicology studies, possibly eliminating the need for a separate pharmacology study
  • The parallel dose study design required in the development of new biologics makes combining structural and functional endpoints logical
  • Provides a more comprehensive assessment of the cumulative effect of a test article on functional endpoints (something not currently required by guidelines)
  • Using animals more efficiently thus supporting the NC3Rs initiative


Publications Validating 24-hour Continuous Monitoring in Toxicology Studies
Validation and utility of the PhysioTel™ Digital M11 telemetry implant for cardiovascular data evaluation in cynomolgus monkeys and Beagle dogs
Cordes, J. S., Heyen, J. R., Volberg, M. L., Poy, N., Kreuser, S., Shoieb, A. M., & Steidl-Nichols, J. (2016, February 1). .

Evaluation of the PhysioTel™ Digital M11 cardiovascular telemetry implant in socially housed cynomolgus monkeys up to 16 weeks after surgery.
Andersen, N. K., Meyer, O., Bradley, A., Dragsted, N., Lassen, A. B., Sjögren, I., … Milne, A. (2017, April 14).



Toxicology Solutions

 









Functional endpoints are collected from conscious, freely moving animals that have a small device implanted into them that is capable of monitoring ECG, Blood Pressure, Temperature, and Activity data and transmitting data to an acquisition and analysis computer system.




JET system



Jacketed External Telemetry (JET) is a non invasive, externally-worn Bluetooth® enabled telemetry device designed for large animal toxicology studies.  JET can be used to monitor ECG, blood pressure (invasive), respiration, temperature and activity.







  

1 level_7 mouse_ pleth_plenum_neb_inflow_photometer



Inhalation systems that deliver absolute or relative doses of smoke, gases, vapor or compounds through nose only or whole body exposure. Monitor respiratory parameters with plethysmography chambers during dosing and after. 




  






Short durations of functional endpoints are collected non-invasively from chemically or physically restrained animals that are connected to external devices capable of monitoring surface ECG or blood pressure and recording directly into an acquisition and analysis computer system.



  



The Ponemah software platform provides powerful tools for toxicologists that ensure Good Laboratory Practice (GLP), CFR Part 11 compliance and SEND format in each and every study.


Why do more researchers choose Ponemah?   

  • Easy study management
  • Versatile and robust acquisition interfaces
  • Accurate and consistent results using automated analysis
  • Advanced GLP compliance with Study Protocol and Data Security Features
  • Smart tools and modules, including SEND, to customize to your study-specific needs
  • And more!



Ponemah software, PNM





From in vitro to in vivo, we've got you covered
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Comprehensive Tox Doc




Peer-Reviewed Toxicology Publications

Determination of LCt50 of aerosolized paraquat and its pulmonary toxic implications in non-anesthetized rats.
Mandal, S. P., Pathak, M. S., Bora, N. K., Patowary, P., Barman, P., Kishor, S., … Chattopadhyay, P. (2018, August 7).


Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.
Bloch-Shilderman, E., Rabinovitz, I., Egoz, I., Yacov, G., Allon, N., & Nili, U. (2017, November 10).



Integrated and translational nonclinical in vivo cardiovascular risk assessment: Gaps and opportunities
Brian R. Berridge, Peter Hoffmann, James R. Turk, Frank Sellke, Gary Gintant, Gerald Hirkaler, KevinDreher, A. Eric Schultze, Dana Walker, Nick Edmunds, Wendy Halpern, James Falls, Marty Sanders, Syril D. Pettit, , Regulatory Toxicology and Pharmacology, Volume 65, Issue 1, February 2013, Pages 38-46, 


Measurement of hyper- and hypotension during repeat dose toxicity studies in either freely moving or physically restrained cynomolgus monkeys.

M. O. Niehoff, B. Niggemann, J. Sternberg, A. Jenkins, M. Holbrook.  Journal of Pharmacological and Toxicological Methods, Volume 70, Issue 3, September 2014, Pages 268-75.

 
Nonclinical safety evaluation of erenumab, a CGRP receptor inhibitor for the prevention of migraine. 
Bussiere, J. L., Davies, R., Dean, C., Xu, C., Kim, K. H., Vargas, H. M., … Monticello, T. M. (2019, May 11).



The physiology and toxicology of acute inhalation phosphine poisoning in conscious male rats.
Wong, B., Lewandowski, R., Tressler, J., Sherman, K., Andres, J., Devorak, J., … Sciuto, A. M. (2017, December 18).