title: Distinguishing between maternally-mediated and directly embryotoxic modes-of-action for postimplantation loss induced in rats by 2-amino-2-methylpropanol.
abstract: In rats, 2-amino-2-methylpropanol (AMP) caused an increase in postimplantation loss in an oral reproductive/developmental toxicity screening assay but not in a dermal developmental toxicity assay. Studies were performed to characterize the mode of action and determine whether the postimplantation loss was a result of direct embryotoxicity or a maternally mediated effect. The studies identified that the postimplantation loss occurs shortly after implantation, has a steep dose response with a clear threshold, requires exposure to AMP for a period of approximately 2-3 weeks prior to gestation and does not involve direct embryo toxicity. The uterine histopathology and gene array analysis of decidual swellings suggested AMP acts via a maternally mediated mechanism affecting the ability of the uterus to support an implanted embryo. Since the postimplantation loss occurs only at maternally toxic doses, the implications for human risk assessment are discussed.
authors.affiliation: Toxicology and Environmental Research & Consulting, Dow Europe GmbH, Horgen CH-8810, Switzerland.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ball
authors.affiliation: Toxicology and Environmental Research & Consulting, The Dow Chemical Company, Midland, MI 48674, USA. Electronic address: rrasoulpour@dow.com.
authors.forename: Reza J
authors.initials: RJ
authors.lastname: Rasoulpour
authors.affiliation: Toxicology and Environmental Research & Consulting, The Dow Chemical Company, Midland, MI 48674, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Zablotny
authors.affiliation: Toxicology and Environmental Research & Consulting, The Dow Chemical Company, Midland, MI 48674, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ellis-Hutchings
authors.affiliation: Toxicology and Environmental Research & Consulting, The Dow Chemical Company, Midland, MI 48674, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Andrus
authors.affiliation: Toxicology and Environmental Research & Consulting, The Dow Chemical Company, Midland, MI 48674, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Carney
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D008297:Male; D033261:Maternal-Fetal Relations / Q000187:drug effects*; D011247:Pregnancy; D011412:Propanolamines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects
chemical_list: D011412:Propanolamines; C006551:2-amino-2-methyl-1-propanol
keywords: 2-amino-2-methylpropanol; CAS RN 124-68-5; Maternally mediated; Postimplantation loss