A Vision for the Future: HuDMOP, the Human Dynamic Multi-Organ Plate
As part of its research program, the Research Institute for Fragrance Materials (RIFM) investigates rigorous and globally accepted New Approach Methodologies (NAMs), which provide alternatives to animal testing to fill data gaps for safety assessment. One of the NAMs currently being tested is the Human Dynamic Multi-Organ Plate (HuDMOP), an in vitro (e.g., non-animal) platform created by IONTOX by LifeNet Health LifeSciences to simulate absorption, distribution, and metabolism across multiple organs.
For RIFM’s pilot project with the HuDMOP, the platform incorporates three plates, with each containing a different medium to simulate a particular organ: the intestine, liver, and kidney. (Other organs may be added in the future). In addition, the platform contains vessels with simulated blood traveling between each “organ.” Scientists first test a material in the HuDMOP to determine nonspecific adsorption by tracking its movement through the system and measuring how much of it is recovered. Then, the amount of intestinal absorption is determined, and the plate medium is checked for cytotoxicity indicators. Once scientists have run a material through the HuDMOP, they can use physiologically based pharmacokinetic (PBPK) modeling to predict additional Absorption, Distribution, Metabolism, and Excretion (ADME) properties and other valuable quantitative information about the material.
Through multi-organ sampling, the HuDMOP may have the potential to provide more realistic insights into ADME than other in vitro tests.
According to RIFM Scientist Dan Selechnik, Ph.D., “The safe use of most fragrance materials for the repeated dose toxicity endpoint can be supported using three possible methods. We can use study data, read-across (using data from one substance to help understand another similar substance), or the threshold for toxicological concern (TTC, a level below which there is no appreciable risk of harm from a fragrance ingredient). However, for those materials that cannot be addressed using these methods, the HuDMOP looks like a promising approach.”