ABSTRACT
Toxicological test methods are necessary to assess the hazard and safety of various substances such as medicines, consumer products, and industrial chemicals. Many of these methods have traditionally used animals as the test system. However, there has been increasing interest in the development of alternative methods that incorporate advances in new science and technology and that utilize knowledge of adverse outcome pathways at the molecular and cellular level [1-3]. New testing methods and strategies are sought that can provide improved accuracy and ef•ciency compared to existing
methods. There are also continuing national and international interests and legislative mandates to develop alternative test methods that can replace animal use, reduce the number of animals required for a test procedure, and re•ne testing procedures to lessen or eliminate unrelieved pain and distress [4]. For any new or revised test method to be used to meet regulatory testing requirements, including alternative methods, the method must •rst undergo adequate validation and then be determined to be acceptable by regulatory authorities. This chapter discusses the criteria and processes for validation and regulatory acceptance of new, revised, and alternative methods and testing strategies. In addition,
De•ning Test Method Performance Standards ................................................................................................................... 1095 Components of Performance Standards ............................................................................................................................. 1095 Process for Developing Performance Standards ................................................................................................................ 1096 Performance Standards for Dermal Corrosivity Test Methods .......................................................................................... 1097 Using Performance Standards for Validation Studies ........................................................................................................ 1098
ICCVAM Role in Validation and Regulatory Acceptance ...................................................................................................... 1098 History ................................................................................................................................................................................ 1098 Purposes and Duties ........................................................................................................................................................... 1098 Test Method Nomination and Submission Process ............................................................................................................ 1099 ICCVAM Contribution to Regulatory Acceptance of Alternative Test Methods ............................................................... 1099
Other Organizations Involved in Validation .............................................................................................................................1100 International Cooperation on Alternative Test Methods .....................................................................................................1100 EURL-ECVAM ...................................................................................................................................................................1100 JaCVAM..............................................................................................................................................................................1100 ZEBET ................................................................................................................................................................................1100
Allergic Contact Dermatitis .....................................................................................................................................................1100 Regulatory Rationale for the LLNA ....................................................................................................................................1101 Mechanistic Basis of Allergic Contact Dermatitis ..............................................................................................................1101 Traditional LLNA Procedure ..............................................................................................................................................1102
