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Paraphenylenediamine (PPD) is one of the main ingredients used in permanent hair dyes. It is, however, known to cause allergic contact dermatitis and potentially serious systemic toxicity. With the increasing popularity of hair dyeing, there is a growing need to address the lack of suitable nontoxic hair dyes for PPD-allergic individuals. Our study examines the safety and efficacy of novel aromatic amines (N1–N7) as potential substitutes for PPD. These compounds were designed and synthesized (a) to have a lower binding affinity to skin proteins to prevent triggering an immune response and cytotoxicity, (b) to have a higher water solubility through the addition of strategic hydrophilic functional groups, and (c) to yield a naturally black color dye without the use of oxidizing agents such as hydrogen peroxide. Generally, hair dyes are intended to tone gray hair to black. About 64% of hair dye users prefer black hair to be dyed in other colors. The commercial hair dye precursor PPD has impeccable dyeing efficacy. It produces black color upon oxidation. To produce other colors, PPD is mixed with several other couplers. Hence, it is paramount to find alternative nontoxic dyes that retain natural black color. Careful structural modification improved the solubility of the compounds from 6.5 to 10%. Hair dye tests showed that oxidized N1–N3 with lower ΔE values (ΔE =2–9.9) resembles natural black hair; further unoxidized forms of the compounds N1–N3, N5, and N7 imparted dark color with ΔE values of 3.7–19.7, suggesting darker dyes in nature. In chemico and in vitro tests revealed that N1–N4 and N6 were weak sensitizers (17.2 ± 2.3% to 22.1 ± 1.7%, respectively) and did not induce IL-8 and IL-1α cytokines’ secretion nor overexpressed CD54 and CD86 sensitization markers in THP-1 dendritic cells. Furthermore, N1–N4 and N6 exhibited nearly three orders of magnitude lower permeation in porcine ear skin compared to PPD. Compounds N1–N4 and N6 displayed a better overall toxicological profile. The O-methyl chain attributes of N1–N4 and N6 play an essential role in improving aqueous solubility, dyeing efficacy, and the safety profile of the new hair dyes. In conclusion, our derivatives are novel, safe, and efficacious permanent alternatives to PPD.