International Regulation of Toxicological Test Systems

Abstract

Toxicity testing for regulatory purposes began after the thalidomide (Contergan®) tragedy in Germany around 1960, when unexpectedly the hypnotic drug caused severe limb malformations in newborns whose mothers had taken the drug during pregnancy. This accident initiated in the first place regulatory testing for drugs, while safety testing of other chemicals, e.g., pesticides, industrial chemicals, cosmetics, and food ingredients, has become mandatory at the international level about 20 years later. Meanwhile regulatory safety testing of chemicals is mandatory in all OECD (Organization for Economic Cooperation and Development, http://www.oecd.org/) member states, which are the major industrial countries except Brazil, China, and India. Initially test requirements as well as individual tests were developed at the national level, and therefore, they differed quite significantly due to experience at the national level of both in industry and regulatory agencies. As a consequence, international industry had to conduct different sets of safety tests to meet the legal requirements in each of these countries. In essence, differences in test requirements created a considerable financial burden both for the industry and also for patients and consumers, who in the end have to pay for testing. Thus, the differences in testing requirements, which were not based on scientific grounds, resulted in barriers to international trade.

Finally, the major industrial nations agreed to correct the situation by harmonizing the safety testing requirements. At the OECD, industry and regulatory agencies took the lead in this activity, since regulatory testing has a higher priority for them than for research-driven academic institutions. It was the goal of the harmonization activity to achieve mutual acceptance of data (MAD) by OECD member countries when the data were produced according to standardized testing requirements. Today harmonization of test guidelines has been achieved for regulatory testing in all areas of toxicology. In addition, the criteria for development and validation of new test methods have been harmonized, since test guidelines have to be updated continuously according to scientific progress and also to meet the needs of testing for newly emerging endpoints.

In this chapter the concept of the mutual acceptance of data (MAD) produced in standardized and harmonized toxicity tests is described and also the criteria for developing, validating, and achieving international acceptance of new tests methods.