Test of the Month!
AcutoX: a human-relevant screen for acute oral toxicity
Dr Tom Ward & Dr Carol Treasure
This month, we’re highlighting AcutoX: our human-relevant screen for acute toxicity. AcutoX was developed by XCellR8 to address an unmet need to replace animal-based LD50 testing, which has been around for 97 years! We live in a very different world now: science and technology has moved on and it’s time to bring acute toxicity testing up to date on both scientific and ethical grounds. So, grab yourself your favourite hot beverage and we’ll take you on a quick trip through the “must-know” aspects of this important topic in the world of safety testing!
A bit of background: why do we need acute toxicity testing?
All chemicals must undergo safety assessment to determine whether they pose a hazard to the user. In general, there are six main hazards that need to be examined for compliance with REACH Annex VII:
- Skin Corrosion – does the chemical have to potential to cause lasting damage to human skin?
- Skin Irritation – if the chemical does not pose a risk of causing lasting damage, can it cause short-term, reversible damage to the skin?
- Skin Sensitisation – is it likely that a user can become allergic to the item?
- Eye Irritation – is it likely that the item will cause damage to the eye?
- Mutagenicity/Carcinogenicity – is the item likely to damage DNA and/or cause cancer?
- Acute Toxicity – how toxic is the item if ingested, inhaled or absorbed through the skin?
Initially, only animal-based methods were developed to examine these hazards; however, today more scientifically advanced and human-relevant tests exist for the majority. For example, at XCellR8 we offer in vitro skin corrosion, skin irritation, eye irritation, and skin sensitisation tests accepted by regulatory bodies worldwide. Other hazards are, unfortunately, still reliant on animal data, so as a company with a mission to accelerate the world’s transition to 100% animal-free testing, we are invested in making sure that in vitro, animal-free solutions are found in these areas.
The development of AcutoX – a human-relevant test
Over the last few years, we have been working on a project to find an in vitro replacement for the animal-based LD50 test for oral acute toxicity, which identifies the amount of chemical sufficient to cause death in 50% of a population of laboratory animals when the item is ingested. While the LD50 test has been used for almost a century, it assumes that an animal, such as a mouse or rat, will react similarly to a human, which often isn’t the case. Many believe that this method is not relevant for the assessment of human health and, for many years, academics and companies such as XCellR8, have been researching ethical, robust, and human-relevant tests to offer the same hazard predictions.
With support from Innovate UK and Animal Aid, we developed AcutoX, a cell-based screen able to predict acute oral toxicity. This method, published recently in the peer-reviewed scientific journal ALTEX, is a human-cell-based test with four different endpoints and includes a metabolic component (human liver fraction “S9”). Just like all tests at XCellR8, AcutoX is free from animal-derived components, maximising the human-relevance of the test. We conducted an internal validation with 68 chemicals with known LD50 values across multiple sectors, such as food, fragrance, pesticides and personal care, and across all hazard categories to obtain the greatest spread of data.
The resulting prediction model can assign GHS and EPA hazard categories. It offers a protective prediction (correct or higher category) in 90.0% and 93.3% of cases for EPA and GHS categories, respectively.
Adoption of AcutoX by industry
Acute toxicity categories have associated hazard statements, such as “Harmful if swallowed”, and warning symbols such as the skull and crossbones or exclamation mark, that are used for labelling of both consumer and industrial products. Currently, animal testing remains the dominant source of data behind these statements. Regulators have encouraged the adoption of in vitro and in silico approaches to acute toxicity assessment.
We hope that the availability of AcutoX makes a major contribution to animal-free safety assessments for this endpoint and a switch to human-relevant science. We are now providing the test to our client companies across industry, who are using it in safety assessment as an animal-free, human-relevant approach for acute toxicity. Data can be included in regulatory submissions as weight of evidence, either alone or in combination with the CATMoS / OPERA in silico approach. Regulatory bodies have welcomed the test as a significant advancement over previous attempts to model acute toxicity in vitro, due to the fully human test system, free of animal-derived components, and the inclusion of a metabolic component.
We are talking to regulatory bodies about next steps to support adoption of the test. To further strengthen our prediction model, we are continuing to invest R&D time and budget into the method with our AcutoX 300 project, through which we’re aiming to test 300 chemicals.
We hope that, in the future, no animals will need to be sacrificed in the name of chemical safety, and that our method, either alone or in combination with other cell-based or computer model data, will be accepted by regulatory bodies for the examination of human acute oral toxicity.
Test of the month
To celebrate our “test of the month”, we’re offering special discounts on our pioneering AcutoX test, for orders placed throughout the month of November. If you’re not ready to test yet, you can place your order now to secure your lab slot and take advantage of the lower price. Discounts vary according to the number of items to test. So, whether you’re trying out this test for the first time, or already familiar with the method, find out more on our website, or contact us to arrange a conversation about how AcutoX can support your animal-free safety assessment process.
Email info@x-cellr8.com
Call +44 (0)1925 607 134.
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