Written by Dr Carol Treasure

What comes to mind when you think of the 1920s? Often known as the “Roaring Twenties”, it was a time of rapid change. People started owning cars and phones, women gained the vote, haircuts and dresses got shorter as many restrictions were cast aside and everyone headed to jazz clubs. It was also a time of unrest, civil war and racism.

Against this wild backdrop, scientist J.W Trevan searched for a way to measure the relative “poisoning potencies” of drugs. He developed the LD50 test because the use of death as a “target” allows comparisons between chemicals that poison the body in very different ways. And so one of the mainstays of animal testing in 20th Century toxicology was born. Millions of animals have since been subjected to severe suffering and death to identify the lethal dose to 50% of them during oral, inhalation or dermal exposure. Scientifically, the LD50 is, at best, the most crude and basic indicator of toxicity, lacking mechanistic information and human relevance, looking at extreme doses with no relevance to real-life exposure.

What about now?

A century later, the world is a very different place, but once again a time of rapid change. As society has moved on, so has science. Now we have organ-on-a-chip poised to revolutionise testing and research, a vast array of sophisticated cell-based assays, reconstructed human tissues, omics technologies, bioprinting, big data and in silico models. One may ask, then, why 80,000 animals are still used for LD50 tests in Europe alone every year, and millions worldwide? 2027 will mark the test’s 100th birthday – surely it’s time we accelerated the moves necessary to consign it to history?

Fortunately, regulators in the US and Europe have encouraged in vitro and in silico methods in combination for acute toxicity. At XCellR8, we wanted to ensure that a highly human-relevant cell-based screen became available. With funding from Innovate UK, EU Horizon 2020 and Animal Aid, we’ve developed AcutoX, now one of the flagship tests we provide to industry sectors from cosmetics to pesticides, to reduce and replace the need for LD50 tests on animals. My personal drive to make an impact in this area goes back to my PhD days, and I’m so proud to see AcutoX making a positive difference.

What is AcutoX?

XCellR8’s GLP-accredited laboratory provides the first truly animal-free preliminary screen for human acute oral toxicity.

Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours).

This test is a non-regulatory human cell-based method, using human dermal fibroblasts in animal product-free culture conditions, and assesses cell membrane integrity (Neutral Red Uptake method) and cell metabolism (MTT method) as an endpoint. The assay includes a human liver extract (S9) to examine the toxifying or detoxifying effect of metabolism on a test item. The output of the test is an IC50 (the dose of cytotoxic compound at which you achieve 50% viability) as an in vitro alternative to the traditional animal-based in vivo LD50. A prediction model is used to place test items into predicted EPA and GHS classifications for human acute oral toxicity.

If you’d like to know more about how AcutoX can support human-relevant safety assessment, please get in contact with our lovely team today, or email info@x-cellr8.com.