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 1 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.
Clode
S A
SA
Covance Laboratories, Harrogate, UK. sally.clode@covance.com
D000726:Androgen Antagonists / Q000032:analysis; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D052244:Endocrine Disruptors / Q000032:analysis*; D004965:Estrogen Antagonists / Q000032:analysis; D004967:Estrogens / Q000032:analysis; D005062:European Union; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis; D051381:Rats; D013963:Thyroid Hormones / Q000097:blood; D023382:Toxicity Tests, Acute / Q000379:methods; D014481:United States; D014484:United States Environmental Protection Agency; D014599:Uterus / Q000187:drug effects
D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D004967:Estrogens; D013963:Thyroid Hormones