Lipophilic toxin pectenotoxin-2 (PTX2) is oxidatively metabolized to pectenotoxin-1 (PTX1), pectenotoxin-3 (PTX3), and pectenotoxin-6 (PTX6) in the Japanese scallop Patinopecten yessoensis. This particular metabolism has been observed only in Japanese scallops, in which PTX6 is the most dominant lipophilic toxin. We investigated the cytotoxicity of PTX2 and its metabolites PTX1,3,6 in a rat cell line (L6) and a human cell line (RD). RD showed an approximately three-fold greater sensitivity than L6 upon exposure to PTXs. The cytotoxicity of PTXs decreased with degree of oxidation in the order PTX2 > PTX1 > PTX3 > PTX6. The calculated half maximal inhibitory concentration (IC₅₀) values of PTX2 obtained for the L6 and RD cell lines were 60 and 23 ng/mL, respectively, while those obtained for PTX6 for both cell lines were over 2,000 ng/mL. These results demonstrate that PTX6 has extremely low cytotoxicity or is non-toxic and that the oxidative metabolism of PTX2 in P. yessoensis is a detoxification process.