The aim of this study was to evaluate the genotoxic effect of a bovine bone-derived hydroxyapatite (HA), Boneplus-xs (B-P-XS). The genotoxicity of B-P-XS was investigated by examining the potential of the xenograft (B-P-XS) to induce gene mutation (evaluated using the Ames test), in vitro chromosome aberration (CA), and sister chromatid exchange (SCE) with tests in cultured human peripheral lymphocytes. Counts of reverse mutations in Salmonella typhimurium TA98 and TA100 strains were not found to be significantly increased after treatment with B-P-XS (P > 0.05). The presence of B-P-XS in peripheral blood culture for 24 and 48 h did not lead to a significant increase in the frequency of CAs (P > 0.05) and SCEs (P > 0.05) when compared to the solvent control (dimethyl sulfoxide). When compared with the control group (untreated), B-P-XS significantly decreased the mitotic index; however, the decrement was not statistically significant when compared with the solvent control in any of the concentrations and treatment times (P > 0.05). In addition, no significant changes in the proliferation index were observed after treatment with B-P-XS when compared to both the control and the solvent control. As a result of this study, we suggest that HA microparticles greater than 200 mu m do not constitute a genotoxic risk for patients undergoing dental surgery.