title: Scientific and Regulatory Policy Committee (SRPC) Points to Consider: Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors.
abstract: The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a multitiered approach to determine the potential for environmental chemicals to alter the endocrine system. The Pubertal Development and Thyroid Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450, 890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream mechanistic pathways along with downstream morphological end points including histological evaluation of the kidneys, thyroid, and select male/female reproductive tissues (ovaries, uterus, testes, and epididymides). These assays are part of a battery of in vivo and in vitro screens used for initial detection of test article endocrine activity. In this Points to Consider article, we describe tissue processing, evaluation, and nomenclature to aid in standardization of assay results across laboratories. Pubertal assay end points addressed include organ weights, estrous cyclicity, clinical pathology, hormonal assays, and histological evaluation. Potential treatment-related findings that may indicate endocrine disruption are reviewed. Additional tissues that may be useful in assessment of endocrine disruption (vagina, mammary glands, and liver) are discussed. This Points to Consider article is intended to provide information for evaluating peripubertal tissues within the context of individual assay end points, the overall pubertal assay, and tier I assays of the EDSP program.
authors.affiliation: Novo Nordisk, Beijing, China.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Keane
authors.affiliation: WIL Research, Hillsborough, North Carolina, USA george.parker@wilresearch.com.
authors.forename: George A
authors.initials: GA
authors.lastname: Parker
authors.affiliation: Regan Path/Tox Services, Inc, Ashland, Ohio, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Regan
authors.affiliation: WIL Research, Hillsborough, North Carolina, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Picut
authors.affiliation: National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina, USA.
authors.forename: Darlene
authors.initials: D
authors.lastname: Dixon
authors.affiliation: Dianne Creasy Consulting LLC, Pipersville, Pennsylvania, USA.
authors.forename: Dianne
authors.initials: D
authors.lastname: Creasy
authors.affiliation: Integrated Laboratory Systems, Raleigh-Durham, North Carolina, USA.
authors.forename: Dipak
authors.initials: D
authors.lastname: Giri
authors.affiliation: The Dow Chemical Company, Midland, Michigan, USA Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Renee R
authors.initials: RR
authors.lastname: Hukkanen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011627:Puberty / Q000187:drug effects*; D051381:Rats; D013960:Thyroid Function Tests / Q000379:methods*; D013961:Thyroid Gland / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D052244:Endocrine Disruptors
keywords: EPA; OPPTS 890.1450; OPPTS 890.1500; endocrine disruptor screening program; pubertal development; thyroid function