title: Gavage-related reflux in rats: identification, pathogenesis, and toxicological implications (review).
abstract: After oral gavage dosing of rats, reflux may occur, resulting in serious respiratory effects and mortality. Published information on gavage-related reflux is limited, as it has not yet been a focus of research. Nevertheless, it represents a recurrent challenge in daily toxicology practice of oral gavage dosing. The absence of clear guidance and criteria for the identification and management of reflux-induced effects can limit the ability to properly interpret toxicity study results. The review presented herein includes an overview of experimental data from gavage studies in rats, in which reflux was observed, and provides a comprehensive analysis of the literature on reflux in general and the different potential pathways contributing to gavage-related reflux in rats. The article aims to increase the awareness and understanding of the pathogenesis of gavage-related reflux and provides guidance on identification of potential risk factors, as well as interpretation of histological changes and their toxicological relevance. Furthermore, differentiation of reflux-induced effects from direct compound-related toxicity and from gavage errors is addressed in particular, and the importance of nasal histology is discussed.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium. SDAMSCH@its.jnj.com
authors.forename: Siegrid
authors.initials: S
authors.lastname: Damsch
authors.forename: Gary
authors.initials: G
authors.lastname: Eichenbaum
authors.forename: Alfred
authors.initials: A
authors.lastname: Tonelli
authors.forename: Lieve
authors.initials: L
authors.lastname: Lammens
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van den Bulck
authors.forename: Bianca
authors.initials: B
authors.lastname: Feyen
authors.forename: John
authors.initials: J
authors.lastname: Vandenberghe
authors.forename: Anton
authors.initials: A
authors.lastname: Megens
authors.forename: Elaine
authors.initials: E
authors.lastname: Knight
authors.forename: Michael
authors.initials: M
authors.lastname: Kelley
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004417:Dyspnea; D004750:Enteral Nutrition / Q000009:adverse effects*; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying; D005764:Gastroesophageal Reflux / Q000378:metabolism / Q000473:pathology*; D009296:Nasal Cavity / Q000473:pathology*; D051381:Rats; D012307:Risk Factors