OTC pharmaceuticals and genotoxicity testing: the paracetamol, anthraquinone, and griseofulvin cases.

Genotoxic effects are hardly assessable in an exposed population but are generally considered to be serious due to their unpredictable effects on subsequent generations and to the link between genotoxicity and cancer. Lack of knowledge about a genotoxic/carcinogenic potential has to be stated for numerous compounds which are often in pharmaceutical use known for a long time. A thorough testing programme like it is done for new compounds is essential for such compounds that are not completely unsuspicious with respect to being reactive with macromolecules or that have the potential to generate reactive metabolites in the body. Paracetamol, anthraquinone-containing preparations, and griseofulvin are examples for pharmaceuticals that have been in use for a long time but for which genotoxicity testing revealed a possible deleterious potential only recently. The Federal Health Office/Federal Institute for Drugs and Medical Devices therefore imposed new studies upon companies marketing these compounds in the last years. These studies in part led to a more thorough description of possible adverse effects or even restrictions for use. Paracetamol exhibits a genotoxic potential in vitro and in vivo probably via indirect, cytotoxicity or enzyme inhibition-mediated effects. Further studies will have to clarify whether a threshold could be established and whether effects do not occur at therapeutic dose levels. Genotoxicity data on the mixed group of anthraquinones reveal positive and negative findings. Compounds such as lucidin, danthron, emodin supposedly have a genotoxic and carcinogenic potential. Further studies with anthraquinone-containing plant preparations will have to clarify the content and genotoxic activity of the preparations and the active ingredients. Lucidin- and danthron-containing preparations are currently no longer in use now whereas restrictions apply for other anthraquinone-containing laxatives. Griseofulvin is acknowledged in the meantime as an aneugen for somatic and germ cells. It is in vitro effective in concentrations that correspond to therapeutic plasma levels.