Assessment of in vivo assays for endocrine disruption

The United States Environmental Protection Agency (USEPA) has developed a screening and testing programme to detect endocrine-disrupting chemicals. This programme is organized into two phases: a tier 1 screening battery and, for those chemicals that are positive in this phase, a tier 2 testing battery. Similarly, the Organization for Economic Cooperation and Development (OECD) has set up a task force to identify, prioritize and validate test methods for the detection of endocrine disrupters. This chapter describes the mammalian in vivo assays recommended by these organizations. The tier I screening recommended by both agencies comprises the uterotrophic assay for the detection of oestrogens and anti-oestrogens, and the Hershberger assay for the detection of anti-androgens. Both of these assays are nearing the end of a comprehensive validation process and show consistency across testing laboratories. A further assay recommended by the USEPA is the female pubertal assay, designed to assess steroidogenesis, anti-thyroid activity and anti-oestrogenicity, while the OECD recommends an enhanced version of their standard regulatory test guideline number 407, the 28-day rat toxicity test. The tier 2 test recommended by both agencies is an enhanced version of the two-generation regulatory study. This is a large time- and animal-consuming study, and in order to obtain the maximum information regarding the potential for endocrine-disrupting activity of a chemical, it should be modified depending on the results of the tier 1 assays.