Toxicological Evaluation of Natural and Synthetic Hair Dyes Containing Paraphenylenediamine (PPD) on Biochemical...

Paraphenylenediamine (PPD) is a primary component of permanent hair dyes and is known for its dermal toxicity; however, systematic dose-response data for chronic exposure are lacking. This study investigated the hepatotoxic and hematotoxic effects of commercial PPD-based dyes using a rabbit model to establish safety thresholds and inform regulatory limits. Seventy-two male rabbits received dermal applications of natural henna (control) or PPD-containing dyes at concentrations of 0.098, 0.187, or 2.375 mg/g every 10 days for 6 months. PPD exposure induced dose-dependent mortality (0% to 22.2%), elevated hepatic enzyme levels (4- to 5-fold increase at the highest dose), and macrocytic anemia (hemoglobin decreased by 28%, red blood cells by 39%). Histopathological analysis revealed progressive hepatocyte damage ranging from mild inflammation to severe necrosis. These findings demonstrate that PPD concentration, rather than the carrier matrix, determines systemic toxicity, and suggest that the current 2% regulatory limit may be insufficiently protective under chronic exposure conditions. This research provides quantitative hazard data for PPD risk assessment and supports the implementation of stricter concentration limits in cosmetic formulations.