title: Pronamide: Weight of evidence for potential estrogen, androgen or thyroid effects.
abstract: Based on the exposure potential to humans and environment, pronamide was one of 52 chemicals on the first list evaluated under US EPA's Endocrine Disruptor Screening Program (EDSP). The purpose of EDSP is to screen chemicals for their potential to interact with estrogen-, androgen-, or thyroid-signaling pathways. A battery of 11 Tier 1 assays was completed for pronamide in accordance with EDSP test guidelines. In addition, Other Scientifically Relevant Information, which included existing data from regulatory guideline studies and published literature, was used in a weight-of-evidence (WoE) evaluation of potential endocrine activity. The WoE conclusion is that pronamide does not interact directly with estrogen, androgen, or thyroid receptors or post-receptor events. Across in vivo studies, the liver is consistently and reproducibly the target organ for pronamide's effects. Pronamide activates hepatocytic nuclear receptors (including constitutive androstane receptor), induces hepatic enzymes, produces hepatocellular hypertrophy and increases liver weights. These changes are coupled with increased metabolic activity and a subsequent increased metabolism and/or clearance of both steroid and thyroid hormones. Thus, while pronamide alters some endocrine-sensitive endpoints in EDSP Tier 1 assays, effects on liver metabolism likely explain altered hormone levels and indirect endocrine changes.
authors.affiliation: The Dow Chemical Company, Midland, MI, USA. Electronic address: mmarty@dow.com.
authors.forename: Mary Sue
authors.initials: MS
authors.lastname: Marty
authors.affiliation: Dow AgroSciences, LLC, Indianapolis, IN, USA.
authors.forename: Sabitha
authors.initials: S
authors.lastname: Papineni
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Coady
authors.affiliation: Dow AgroSciences, LLC, Indianapolis, IN, USA.
authors.forename: Reza J
authors.initials: RJ
authors.lastname: Rasoulpour
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: Lynn H
authors.initials: LH
authors.lastname: Pottenger
authors.affiliation: Dow AgroSciences, LLC, Indianapolis, IN, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Eisenbrandt
mesh_terms: D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D042341:Gonadal Hormones / Q000378:metabolism; D006065:Gonadotropins, Pituitary / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D001549:Benzamides; D052244:Endocrine Disruptors; D042341:Gonadal Hormones; D006065:Gonadotropins, Pituitary; D006540:Herbicides; D013963:Thyroid Hormones; C001059:pronamide
keywords: Androgen; Endocrine; Endocrine Disruptor Screening Program (EDSP); Enzyme induction; Estrogen; Pronamide; Testosterone metabolism; Thyroid; Thyroxine metabolism