A Timetable for Replacing, Reducing and Refining Animal use with the Help of in Vitro Tests: The Limulus Amebocyte Lysate Test (LAL) as an Example

2 Outside of regulations, outside of imaginations

“…Despite its later celebration as a 'unique example of a successful in vitro replacement of an animal toxicity test', 39 the LAL test was 'not discovered as a result of a directed effort to develop an alternative to the rabbit pyrogenicity test'. 40 This contrasts with how LAL is marketed by many companies today. For example, Charles River Laboratories argue: 'The in vitro Limulus Amoebocyte Lysate (LAL) test was developed in the 1970s, as part of a 3Rs initiative to replace the need to use hundreds of thousands of rabbits each year in the testing of human and animal products for contamination'.…”

“…36 Similarly, Flint suggests that 'the LAL test, fulfils the objectives of reducing, refining and replacing animals in medical experiments'. 37 The move to LAL for bacterial endotoxin testing certainly enabled the phasing out of large colonies of rabbits, producing a significant reduction in harm to animals -and to the technicians responsible for injecting the rabbits with samples. However, as Zhang notes, 'the LAL test still required the use of animals, but the grisly process of sticking needles into animals became hidden and outsourced to a different part of the supply chain'.…”

Novel Pyrogen Tests Based on the Human Fever Reaction

“…These drugs cannot reasonably be tested in rabbits. The solution was the LAL test (33)(34)(35) which, over the last 30 years, has replaced the rabbit pyrogen test for these and a number of other products (36)(37)(38).…”