Obtaining new cosmetic ingredients, mainly from sustainable sources, as novel excipients or even active compounds is noteworthy for the cosmetic industry to enhance new innovative dermocosmetics. Thus, it is essential to establish the safety of these new ingredients to avoid adverse events, mainly those associated with clastogenic effects from the chemical compounds used for collagen extraction. In this study, we evaluated solutions of chemical compounds used in the collagen extraction process from tilapia skin (Oreochromis niloticus). The cytotoxic and genotoxic effects of the solutions used in the collagen extraction process were 10.0, 1.0, 0.5, and 0.1% n-butanol. Solutions were evaluated by the Allium test and the comet assay in peripheral white blood cells. The residual water from the final skin wash in the pre-treatment phase and the 0.5% lyophilized collagen extract were also investigated. The absence of cytotoxic and genotoxic activity was demonstrated in the collagen extract, despite the fact that n-butanol showed DNA damage, both in the root cells of Allium cepa and in the white blood cells of human peripheral blood. Therefore, we note the necessity to carry out genotoxicity tests to guarantee the absence of contaminants in the collagen extract for cosmetic purposes.