Human systemic exposure to [(14)C]-paraphenylenediamine-containing oxidative hair dyes: Absorption, kinetics, metabolism, excretion and safety assessment.

•We measured human systemic exposure to two dark-shade, commercial oxidative hair dyes containing 1.0 or 2.0% [14C]-paraphenylene diamine (PPD).•Systemic exposure amounted to 0.72 or 0.88% of the applied amount of [14C]-PPD in subjects exposed to 1.0 or 2.0% PPD, respectively.•Only a single metabolite (N,N′-diacetyl-PPD) was found in human plasma and was also predominant in the urine.•A toxicokinetic-based safety assessment calculated a margin of safety of ≥23.3-fold, when the human plasma AUC value was compared with that of rats at the NOAEL of PPD (8 mg/kg/day).•Given that humans are exposed to oxidative hair dyes intermittently and both humans and rats are exposed to the same metabolite, PPD-containing oxidative hair dyes pose no systemic health risk.