title: Assessment of cervical passage of vital dyes in pregnant, nonpregnant, and mated rats and mice.
abstract: Risk assessment for indirect exposure to small molecule pharmaceuticals in semen to the conceptus has traditionally been handled by calculations based on assumptions that any embryo-fetal exposure would be secondary to maternal absorption and redistribution. This study was designed to assess the potential for transcervical passage of drugs from semen. Reproductive tracts of rodents were examined following vaginal dosing with vital dyes during the estrous cycle, mating, and pregnancy. Toluidine Blue was not observed beyond the cervix after vaginal administration in pregnant rats; additionally, it did not pass the cervix in rats during any phase of estrous. In order to address the effects of semen, rats were dosed at receptivity and mated. Vital dyes were not visually evident in the uterus despite vaginal and sperm plug staining. This study provides evidence that direct transcervical passage is not a substantial route of direct embryo-fetal exposure for small molecule drugs in semen.
authors.affiliation: Department of Reproductive Toxicology, Drug Safety Evaluation, Research & Development, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA. Electronic address: kary.thompson@bms.com.
authors.forename: Kary E
authors.initials: KE
authors.lastname: Thompson
authors.affiliation: Department of Reproductive Toxicology, Drug Safety Evaluation, Research & Development, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Rayhon
authors.affiliation: Preclinical Development & Safety, Janssen Research & Development, 2340 Beerse, Belgium.
authors.forename: Graham
authors.initials: G
authors.lastname: Bailey
authors.affiliation: Preclinical Development & Safety, Janssen Research & Development, 2340 Beerse, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Delille
authors.affiliation: Department of Reproductive Toxicology, Drug Safety Evaluation, Research & Development, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: McNerney
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism*; D004396:Coloring Agents / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D008297:Male; D018811:Maternal Exposure; D008813:Mice, Inbred ICR; D018812:Paternal Exposure; D010539:Permeability; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D012661:Semen / Q000378:metabolism*; D012726:Sexual Behavior, Animal; D013997:Time Factors; D014048:Tolonium Chloride / Q000008:administration & dosage / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism
chemical_list: D004396:Coloring Agents; D014048:Tolonium Chloride
keywords: Cervical passage; Intravaginal; Risk assessment; Semen; Vital dyes