<p>Comprehensive studies on the acute toxicity and safety profiles of therapeutic doses of ¹⁶⁶Ho-EDTMP and ¹⁶⁶Ho-DOTMP in the bone tissue and bone marrow of animals are limited, particularly when ¹⁶⁶Ho produced in low-power reactors is used. These bone-specific complexes were synthesized through the coordination of ¹⁶⁶Ho³⁺ ions in a neutral buffer. Acute toxicity studies were conducted at a dose of 1850 MBq/kg over 14 days, whereas safety assessments were performed at therapeutic doses of 18.5, 37, and 74 MBq/kg over 30 days in ICR mice. Hematological, biochemical, and histopathological toxicities were evaluated. ¹⁶⁶Ho was obtained with high specific activities and radionuclide purity. These radiolabeled ligands were prepared with high radiochemical purity. No unexpected acute toxicity was observed. In the study groups, there were no significant signs of toxicity in the hematological, biochemical, or histopathological evaluations. However, a minimal reduction in osteocytes and osteoblasts in the bone marrow was noted. Notably, densely active hematopoiesis and progenitor clusters, including megakaryocytes, myeloblasts, and lymphoblasts, were observed in the bone marrow of the femurs and sternums. These findings provide valuable insights into the safety profiles of these radiolabeled ligands for bone and bone marrow, supporting further preclinical evaluations and domestic applications.</p>