The safety of highly purified fullerenes (HPFs) for utilization as antioxidants in the cosmetic industry was evaluated by studying the toxicity and effects on laboratory animals, human epidermal keratinocytes, and human fibroblasts. The HPFs did not induce primary or cumulative skin irritation, skin sensitization, skin photosensitization or contact phototoxicity. No skin reaction was observed in the patch test on human skin. In the primary eye-irritation test on rabbits, conjunctival redness and corneal epithelial defects were observed in all animals of the eye-unwashed group at 1 and 24 hr after application, but disappeared by 48 hr after application. The irritation may have been caused by administration of insoluble fullerene powder. Therefore, the HPFs were assessed as “minimally irritating” in the eye-irritation test. By comparing these results with previously published data, we concluded that HPFs can be safely used in cosmetic ingredients for human skin application. This is the first study performing all the toxicity tests on the same fullerene material for approval as an additive in quasi-drugs.