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Unexpected nasal changes in rats related to reflux after gavage dosing. | LitMetric
In a three-week oral gavage toxicity study in rats, a high incidence of respiratory symptoms and high mortality was noted in compound-dosed rats only. Because of audible respiration, an effect in the upper respiratory tract was suspected and the nasal cavity was included for examination. Histology revealed extensive necrosis and purulent inflammation within the nasal passages, indicative of direct irritation. Since posterior nasal regions were most affected, with food material present within the inflammatory exudates, reflux and retrograde aspiration of irritant material (possibly stomach contents with test formulation) into the nasal cavity were suspected. Lowering the dose volume and fasting the rats prior to gavage dosing substantially reduced the respiratory effects and mortality. The current article focuses on the histological changes in the nasal cavity indicative of gavage-related reflux and provides guidance on differentiation between technical gavage error and gavage-related reflux.
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