IVAL’s MetMax™ Technology Wins EPA’s Transform Tox Challenge

IVAL’s MetMax™ system has been selected as one of the five winners in the Transform Toxicity Challenge by National Toxicology Program (NTP) and the United States Environmental Protection Agency (EPA).

High-throughput screening (HTS) assays are deployed to rapidly test whether some of the thousands of chemicals in use may affect human health. However, current HTS assays do not fully incorporate chemical metabolism, often neglecting compounds that are metabolized to more toxic forms. The Transform Toxicity Testing Challenge was launched by EPA in January 2016 to seek novel technologies that can capture the key toxin metabolizing information.

In November 2017, IVAL’s MetMax™ technology was chosen as one of the five winners by producing “Practical designs that bring us one step closer to turning existing, commonly used in vitro high-throughput chemical screening assays into tests which evaluate both parent chemical and metabolite effects in the assay responses”.

MetMax™ Human Hepatocytes (MMHH; patent pending), was developed as a convenient experimental reagent to provide hepatic metabolism to in vitro toxicity assays, including cytotoxicity and genotoxicity.

MMHH are cryopreserved permeabilized human hepatocytes supplemented with phase I and II drug metabolizing enzyme cofactors. MMHH has metabolic activities similar to conventional cryopreserved human hepatocytes, but with the conveniences of cell-free fractions such as -80 degree storage and direct thaw-and-use protocol. After thawing, MMHH can be directly added to the wells of the target cells as an exogenous metabolic system, allowing scientists to evaluate toxicants whose toxic potential was impacted by metabolism. MMHH were compatible with all high throughput screening multi-well systems, including 24, 48, 96, 384, and 1536 well plates. The permeabilized membranes of MMHH allowed ready interaction of hepatic drug metabolizing enzymes with the test compounds as well as ready diffusion of the resulting hepatic metabolites from the hepatocytes to interact with the target cells.

Proof-of-concept studies were performed on HEK 293 cells, a cell type that is not competent in xenobiotic metabolism with model pro-toxicants. Study showed that the cytotoxicity of model compounds in HEK 293 cells was significantly enhanced by the presence of MMHH, and that the metabolic enhancement could be abolished by heat-inactivation of MMHH.

MetMax™ Human Hepatocytes represent a promising experimental system to provide exogenous hepatic metabolism to in vitro toxicity assays that do not possess metabolic capacity.

For more information on IVAL’s MetMax™ Hepatocyte and Enterocyte products, please go to: MetMax™ Products

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