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This study investigates for the first time in vivo potential release of bound microcystins (MCs) from edible fish tissues. Bound MCs were released in the mouse digestive system and reached the liver (2.1–14.3 ng g−1) and blood (1–5 ng ml−1). The released MCs were active and negatively affected liver functions of treated mice. The estimated daily intake (EDI) for bound MCs (93.5 μg kg−1 day−1) is about 2300 times higher than the WHO safe EDI (0.04 μg kg−1 day−1), compared to lower EDI for free MCs (0.002 μg kg−1 day−1). Therefore, bound MCs in fish tissues should be considered when fish are monitored for human consumption.Bound MCs can be released in the mouse digestive system.Released MCs are active and affect mouse liver functions.Bound MCs could increase the toxin burden in human upon fish consumption.