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(63-01) Development of a test system to evaluate endocrine effects in birds. Leopold, Annegaaike*,1, Bennett, Richard2, Springer, Timothy3, Brugger, Kristin4, 1 Wildlife International - European Office, Warnsveld, The Netherlands2 Office of Research and Development - US Environmental Protection Agency, Duluth, MN3 Wildlife International Ltd, Easton, MD4 DuPont Agricultural Products, Newark, DE ABSTRACT- An overview of the process and status of the development of one and two generation Japanese quail reproduction studies for regulatory use will be presented from the perspective of members of the subgroup of the OECD Expert Group on Assessment of Endocrine Disrupting Effects in Birds. The overall objective of the two-generation test is to characterize endocrine and other toxic effects on the development and reproduction of birds over two generations. However, this objective is open to so many interpretations that it provides little direction for test development. Thus, it has proven useful to attempt to identify a number of conceptual corner-stones or premises to provide a working definition of the purpose of the test and the boundaries of the problem. In the OECD Expert Group, a number of crucial conceptual issues could be identified, and certain premises were easily agreed upon, whereas other conceptual issues presented dichotomies that were difficult or impossible to resolve given present knowledge of biology, methodologies, and regulatory needs. The agreed premises and unresolved dichotomies will be described, and reasons for lack of agreement will be explored, including unresolved methodological issues crucial to the development of a two-generation toxicity test. Advantages and disadvantages of alternative approaches, and tests proposed to resolve these issues during the pre-validation phase of this process will be presented. Various issues that will be discussed include: 1) the timing and duration of dietary exposure over two generations, 2) the suite of fitness and other endocrine-related endpoints to be used and how they are interrelated, 3) the use of hypothesis testing to determine NOAELs vs defining dose-response relationships, 4) methods for selection of F1 chicks for the breeding populations, and 5) choosing between the use of a constant dietary concentration for all life stages or a constant ingested dose. Key words: avian, endocrine, quail, method |
