Toward internal threshold for toxicological concern: in vitro hepatocyte metabolism testing of 207 chemicals using cryopreserved suspended hepatocytes for physiologically based pharmacokinetic modeling

Description

Ellison and colleagues measure how fast liver cells clear 207 chemicals, data needed to set an internal safety threshold for exposures. Safety limits today rest on doses fed to animals, but harm depends on the level that reaches blood and tissue. Their 2026 study uses frozen, thawed liver cells from several species at two low doses. The clearance rates feed body simulation models that convert no effect doses in animals into internal exposure estimates.

Clearance varied hugely across chemicals, from none to very fast, yet about two thirds of chemicals cleared slowly at both doses. Rates at the two doses tracked each other closely, which supports the assay's reliability. The data will help regulators judge combined exposures from food, skin, and air together. They can screen exposures from many routes at once and read the chemical traces found in people's blood, all with fewer new animal tests.

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Source: https://europepmc.org/article/MED/PMC13476076