title: Human systemic exposure to [¹⁴C]-paraphenylenediamine-containing oxidative hair dyes: Absorption, kinetics, metabolism, excretion and safety assessment.
abstract: Systemic exposure was measured in humans after hair dyeing with oxidative hair dyes containing 2.0% (A) or 1.0% (B) [(14)C]-p-phenylenediamine (PPD). Hair was dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected for 48 hours after application. [(14)C] was measured in all materials, rinsing water, hair, plasma, urine and skin strips. Plasma and urine were also analysed by HLPC/MS/MS for PPD and its metabolites (B). Total mean recovery of radioactivity was 94.30% (A) or 96.21% (B). Mean plasma Cmax values were 132.6 or 97.4 ng [(14)C]-PPDeq/mL, mean AUC(0-∞) values 1415 or 966 ng [(14)C]-PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [(14)C] mainly occurred within 24 hrs after hair colouring with a total excretion of 0.72 or 0.88% of applied radioactivity in studies A or B, respectively. Only N,N'-diacetylated-PPD was detected in plasma and the urine. A TK-based human safety assessment estimated margins of safety of 23.3- or 65-fold relative to respective plasma AUC or Cmax values in rats at the NOAEL of a toxicity study. Overall, hair dyes containing PPD are unlikely to pose a health risk since they are used intermittently and systemic exposure is limited to the detoxified metabolite N,N'-diacetyl-PPD.
authors.affiliation: L'Oréal Research and Innovation, Worldwide Safety Evaluation, Asnières sur Seine, France. Electronic address: nepomuk@noos.fr.
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Nohynek
authors.affiliation: The Procter & Gamble Company, Mason, OH, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Skare
authors.affiliation: TNO, Zeist, The Netherlands.
authors.forename: Wim J A
authors.initials: WJA
authors.lastname: Meuling
authors.affiliation: The Procter & Gamble Company, Global Analytical Capability, Mason, OH, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Wehmeyer
authors.affiliation: TNO, Zeist, The Netherlands.
authors.forename: Albertus Th H J
authors.initials: ATHJ
authors.lastname: de Bie
authors.affiliation: TNO, Zeist, The Netherlands.
authors.forename: Wouter H J
authors.initials: WHJ
authors.lastname: Vaes
authors.affiliation: L'Oréal Research and Innovation, Worldwide Safety Evaluation, Asnières sur Seine, France.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Dufour
authors.affiliation: Kao Corporation, Darmstadt, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Fautz
authors.affiliation: Henkel AG & Co. KGaA, Düsseldorf, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Steiling
authors.affiliation: Procter & Gamble Service GmbH, Schwalbach am Taunus, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Bramante
authors.affiliation: L'Oréal Research and Innovation, Worldwide Safety Evaluation, Asnières sur Seine, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Toutain
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002247:Carbon Isotopes; D002851:Chromatography, High Pressure Liquid; D003257:Consumer Product Safety; D005260:Female; D006197:Hair / Q000737:chemistry / Q000187:drug effects; D006202:Hair Dyes / Q000737:chemistry*; D006801:Humans; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D010655:Phenylenediamines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D002247:Carbon Isotopes; D006202:Hair Dyes; D010655:Phenylenediamines; C029728:4-phenylenediamine
keywords: Consumer exposure; Hair dyes; Margin of safety; Paraphenylenediamine; TK-based safety assessment; Toxicokinetics