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In Vivo Neurotoxicity

There are various in vitro systems that produce data for evaluating potential neurotoxic effects, including primary cell cultures, cells lines, cloned cells, and so on. While they are important in studying the mechanism of action, their role in neurotoxic detection in human health risk assessment has not been identified to any great extent, because in vitro methods can hardly consider the route of administration, the distribution of the toxicant in the body, or the metabolism of substance. The neurotoxic effects obtained from in vitro systems usually require the further in vivo data from intact animals to enhance the reliability of the results. Multiple goals should be achieved in the neurotoxic identification process, including the delineation of the mechanisms of neurotoxicity and pathogenesis, the generation of pharmacokinetic data, the evaluation of the relationship between potential maternal and developmental toxicity, the elucidation of the altered function or pathological changes, the determination of neurotoxic effects after recurrent exposures, and the address of potential drug interactions. And most of them need to be performed or validated in appropriate animal models.


Our In Vivo Neurotoxicity Assays
Creative Animodel provides an integrated battery of in vivo neurotoxicity assays, roughly divided into four categories: acute and subchronic neurotoxicity assays, developmental neurotoxicity, liability assays, and local neurotoxic assays.

Acute and Subchronic Neurotoxicity Assays
Both acute and subchronic neurotoxicity assays are contained in our portfolio for the perfection of in vivo neurotoxicity in compliance with guidelines. Functional Observational Battery (FOB), locomotor activities, neuropathological and functional evaluations are performed in both studies: EPA acute neurotoxicity battery and subchronic neurotoxicity.
Developmental Neurotoxicity
The developing central nervous system is more vulnerable to injury than maternal one. We focus on clinical observations, functional tests, and neuropathology. The functional tests involve measurements of developmental landmarks and reflexes, auditory startle test, motor activity, learning and memory tests, and neuropathology.
Liability Assays
Abuse liability and seizure liability are potentially serious adverse effects, probably leading to a drug failure. Our in vivo abuse liability studies include but are not limited to drug self-administration, drug discrimination, and physical dependency. We provide seizure liability assay based on mouse EEG (electroencephalography) models that give a high prediction accuracy.
Local Neurotoxic Assays
We provide CNS behavioral testing, nerve conductance test, and EthoVision to evaluate locally functional and pathological effects. We can perform both FOB and Irwin tests recommended by ICH (International Council for Harmonisation) to identify potential CNS adverse effects of test drugs. EthoVision is a versatile technique to track and analyze the behavior, movement, and activity of animals. Nerve conductance test (NCS) is commonly used to measure how fast an electrical impulse moves through the nerve, hence to identify nerve damage.

Additionally, Creative Animodel also provides specialty in vitro toxicology services. We have strong expertise in offering both standard and custom pharmacological assessments in compliance with FDA and EMA guidelines. We are looking forward to the cooperation with you in the near future.

1. Giordano, G.; Costa, L.G. Developmental neurotoxicity: some old and new issues. ISRN toxicology, 2012 (2012).
2. Healy, C.E.; et al. Acute and subchronic neurotoxicity studies with tri-n-butyl phosphate in adult Sprague-Dawley rats. American Industrial Hygiene Association, 1995, 56(4): 349-355.

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45-1 Ramsey Road, Shirley, NY 11967, USA 1-631-614-7828 1-631-372-1052 Europe 44-207-097-1828

Creative Animodel

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