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Background: Sodium hypochlorite (NaOCl) is the most widely used endodontic irrigant because of its excellent antimicrobial, organic tissue dissolving, and lubricating properties. However, it is highly cytotoxic to the periapical tissues. Aim: This study evaluated in vitro the extrusion of 5.25% NaOCl through the apical foramina of mesiobuccal (MB) root canals of maxillary first molars in two experimental conditions: Before apical debridement and after apical debridement with different instrument sizes to ensure direct access to the apical foramen (apical patency). Materials and Methods: Coronal accesses were prepared in 17 teeth and the apical foramina of the distobuccal and palatal root canals were sealed. The teeth were held in acrylic receptacles with the roots turned upwards to reproduce their position in the maxillary dental arch. The receptacles were filled with a starch/KI solution (a reagent that changes its color to blue after contacting NaOCl) covering the roots. The experiment had two phases: P1: Irrigation of the MB canals with 5.25% NaOCl without previous establishment of apical patency; P2: Canal irrigation after use of size 10 K-file and size 15 Flexofile as patency files. Only specimens with no NaOCl extrusion in P1 were assigned to P2. NaOCl was delivered pressureless at the canal entrance. The moment that the starch/KI solution contacted NaOCl was captured on digital photographs. Results and Conclusions: There was no NaOCl extrusion in nine specimens in P1, but all of these teeth had irrigant extrusion in P2. The 5.25% NaOCl used as an endodontic irrigant showed great capacity to extrude beyond both intact and small-sized apical foramina of MB root canals of maxillary first molars. [ABSTRACT FROM AUTHOR]