Expertly evaluating toxicological processes across species to determine the relevance to man
Since 2001, we have worked collaboratively with clients to design and perform mechanistic investigations to understand the human relevance of rodent toxicological findings.
Our adept scientists have recognized expertise in investigating rodent toxicology and its relevance to humans. By understanding the pathways that define the sensitivity of cells to chemicals, we evaluate the actual hazard to man.
As an example, chronic activation of the nuclear hormone receptors CAR/PXR or PPARα in lifetime rodent carcinogenesis studies can lead to the development of liver tumors. Phenobarbital (PB) is one such molecule. Chronic exposure to PB does not cause liver cancer in humans as the mechanism is unique to rats and mice and is not considered to be relevant for humans. Demonstration that rodent liver tumors observed in chronic studies develop via a phenobarbital (PB)-like mechanism can lead to a non-carcinogenic classification. Using this approach, it is possible to prevent or reduce a carcinogenic classification.
Events that lead to adaptive changes in rodent liver often result in secondary toxicity in the thyroid or testes. If thyroid or testicular tumorigenesis is secondary to a PB-like liver carcinogenesis, then these tumors are not considered relevant to humans. Should this occur, our skilled scientists have experience and expertise in evaluating the mechanism of action (MOA) and building the relevant investigations into the mechanistic studies.
We are dedicated to solving issues relating to the safety of compounds via our collaborative approach and cutting-edge expertise. We will work with you to design state-of-the-art investigative studies to understand the mechanism of action (MOA), interpret the results and make recommendations to lead you to success.
Human relevance toxicology capabilities
Our unique approach is used to:
- Evaluate the existing data set and develop a biologically relevant hypothesis
- Design and run the studies to:
- Confirm the hypothesized mechanism of action
- Confirm the specificity of the nuclear receptor involved using transgenic animals or cells unique to Concept
- Model the MOA in primary hepatocytes
- Perform the human relevance in primary human hepatocytes
- Analyze and interpret the data
- Provide technical support for data defense