From Alternative Methods to a New Regulatory Toxicology

In the last 150 years, chemists have synthesized about 70 million substances. More than 100,000 of these are found in consumer products of daily use, in drugs, in cosmetics, in detergents, in our food, our clothes and – last but not least – as contaminants of our natural environment. When Bayer brought AspirinTM – our eldest synthetic drug – to the market 111 years ago, no regulatory safety assessments on animals were stipulated by legislation. The producer was held liable for any problems with his products. This did not always turn out as positive as in case of aspirin; only a few days after aspirin, the same chemist, Felix Hoffmann (1868-1946), synthesized a sedative for coughs: heroin... (Fig.1). Not every product is as harmless as aspirin. It is easy to understand that, with each safety scandal, the desire for safety assessments grows. In the 1920s, scientists started to use mice and rats broadly for laboratory research. Until then, it was considered absurd that these animals could mirror humans. It was clearly convincing, however, just how fast experiments could be performed with them: the animals did not cost a lot, they reproduced quickly, and a large number of them could be kept in a small cage. This created a real research rush, similar to today’s introduction of stem cells. With every scandal the toolbox of toxicology grew as chemists sought to prevent a similar occurrence. In the early 1930s in the US LashLure created a scandal: The cosmetic product was used to dye lashes permanently; unfortunately, the anilin dye it contained sometimes led to strong inflammation. More than 3,000 reports of collateral effects were collected: five women were blinded, and one woman died. This prompted the first regulation of cosmetics, which have since been controlled in the US by the FDA (Food and Drug Administration). Their employee, John H. Draize (1900-1992) in 1944 developed the Draize rabbit eye test, where a chemical is applied into the eye of a rabbit (Hartung et al., 2010). Today, many perceive this procedure as cruel, but in fact, for 65 years this test prevented the recurrence of a case like LashLure. In this manner, toxicology grew with every scandal, pieced together like a patchwork quilt. From Alternative Methods to a New Regulatory Toxicology