title: Analysis of EPA's endocrine screening battery and recommendations for further review.
abstract: EPA's Endocrine Disruptor Screening Program Tier 1 battery consists of eleven assays intended to identify the potential of a chemical to interact with the estrogen, androgen, thyroid, or steroidogenesis systems. We have collected control data from a subset of test order recipients from the first round of screening. The analysis undertaken herein demonstrates that the EPA should review all testing methods prior to issuing further test orders. Given the frequency with which certain performance criteria were violated, a primary focus of that review should consider adjustments to these standards to better reflect biological variability. A second focus should be to provide detailed, assay-specific direction on when results should be discarded; no clear guidance exists on the degree to which assays need to be re-run for failing to meet performance criteria. A third focus should be to identify permissible differences in study design and execution that have a large influence on endpoint variance. Experimental guidelines could then be re-defined such that endpoint variances are reduced and performance criteria are violated less frequently. It must be emphasized that because we were restricted to a subset (approximately half) of the control data, our analyses serve only as examples to underscore the importance of a detailed, rigorous, and comprehensive evaluation of the performance of the battery.
authors.affiliation: Monsanto Company, St. Louis, MO, USA. Electronic address: adam.schapaugh@monsanto.com.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Schapaugh
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: McFadden
authors.affiliation: Bayer CropScience, Research Triangle Park, NC, USA.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Zorrilla
authors.affiliation: Bayer CropScience, Research Triangle Park, NC, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Geter
authors.affiliation: Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Leah D
authors.initials: LD
authors.lastname: Stuchal
authors.affiliation: Department of Health, West Chester University, PA, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Sunger
authors.affiliation: Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA; Applied Pharmacology and Toxicology, Inc., Gainesville, FL, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Borgert
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D003530:Cyprinidae / Q000502:physiology; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency; D014599:Uterus / Q000187:drug effects / Q000254:growth & development; D014981:Xenopus / Q000502:physiology
chemical_list: D052244:Endocrine Disruptors; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase
keywords: Assay; Endocrine Disruptor Screening Program; Hormone system; Tier 1 Endocrine Screening Battery