WHY TOXICOLOGY IS CHANGING
The concept of our new toxicology testing programme is based on a ground breaking publication released by the National Research Council USA (NRC) in 2007. This publication was commissioned by the U.S Environmental Protection Agency “to review the state of the science and create a far-reaching vision for the future of toxicity testing.”
With this, the NRC adopted a new way of thinking - how could toxicology be revolutionised to test complex mixtures of thousands of chemicals that have already been released into the environment?
The current traditional methods for toxicological testing, some of which use animals, are expensive, slow and may have limited relevance to humans. The NRC have therefore recommended moving away from animal testing to using recent scientific advances and focus on high throughput in-vitro assays using human cells. Human derived cells and reconstructed human tissues have been shown to better model humans. These assays can be conducted quickly with multiple replications which helps to increase confidence in the results.
Imperial Brands does not conduct tests or research on animals.
HOW IS IMPERIAL BRANDS APPLYING THIS METHODOLOGY?
Imperial Brands do not commission or conduct research involving animals, and would not undertake such research unless required to do so by governments or recognised regulatory authorities. Our Toxicology Testing programme provides alternative assays and research tools to assess product safety without using animals. This will allow us to assess the safety of products in relation to a number of diseases caused by smoking, including cancer and chronic obstructive pulmonary disease (COPD).
Recently, we have begun to expand the range of assays we can perform either in-house or with our external contract research organisations. We test our products using a variety of assays summarised in the schematic below. This gives us an in depth knowledge of our products, enabling our team of toxicologists and product & health scientists to better understand potential effects of our products on human cells.
Another benefit of these techniques is their flexibility – with Next Generation Product (NGP) technology continuing to develop, having a wide range of assessment tools enables us to pursue our vision of cutting edge product design and performance.
These are just two examples of the new assays we use:
One area we have looked into is the effect of e liquids from our subsidiary Fontem Ventures on human cells.
The health of cells that line vessels and arteries in the body and their ability to repair is important for cardiovascular health. Cigarette smoke has been shown to delay cell repair in in vitro* models. Therefore, a model has been developed externally to assess the effect of different products on cell repair. This allows us to determine the effect of our products on cell health. The same equipment can also be used to investigate increased white blood cell attachment to vessel walls, another reported early indicator of cardiovascular disease.
In this assay, e liquid vapour is applied to cells in a petri dish. The cells are then ‘scratched’, the time for repair measured, and compared to the time taken for cells to repair when exposed to cigarette smoke. This assay allows us to compare the effects of different products and product modifications on cell repair time. The video shows the scratch closing.
MEASUREMENT OF CILIA MOVEMENT
Cilia are small hair-like structures in the lungs which are important for removing mucous. Reduced mobility of cilia in the deeper parts of the lung can lead to a retention of mucous. Mucous retention has been associated with lung diseases including Chronic Obstructive Pulmonary Diseases (COPD).
This assay measures the impact of a product, such as e liquid, on cilia movement (speed and functionality) on human lung cells by evaluating the impact of different exposures on the frequency at which the cilia move.
High speed cameras are used to record the effects of different products on the cilia in 3D human lung cells. Excessive mucous in the lung model following product exposure can also be viewed by specific stains under a light microscope. A project to develop this COPD model is part of a cross industry collaboration in conjunction with other tobacco manufacturers, regulatory bodies (Food and Drug Administration (FDA) in the USA), and the Institute for In Vitro Sciences (IIVS).
The circular movement in the top left of the video illustrates how cilia move mucous. The cilia in the video are beating at 10 times per second.
Our aim is to develop a robust COPD model for product assessment and regulatory submissions.
Ultimately, we aim to use the knowledge gained in tests like these to support the development of new and potentially safer products.
*In vitro refers to experiments conducted on cells in a petri dish.