Title
Human systemic exposure to [14C]-paraphenylenediamine-containing oxidative hair dyes: Absorption, kinetics, metabolism, excretion and safety assessment
Author
Nohynek, G.J.
Skare, J.A.
Meuling, W.J.A.
Wehmeyer, K.R.
de Bie, A.T.H.J.
Vaes, W.H.J.
Dufour, E.K.
Fautz, R.
Steiling, W.
Bramante, M.
Toutain, H.
Publication year
2015
Abstract
Systemic exposure was measured in humans after hair dyeing with oxidative hair dyes containing 2.0% (A) or 1.0% (B) [14C]-p-phenylenediamine (PPD). Hair was dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected for 48 hours after application. [14C] 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 [14C]-PPDeq/mL, mean AUC0-∞ values 1415 or 966 ng [14C]-PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [14C] 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. © 2015 Elsevier Ltd.
Subject
Life Triskelion BV
MSB - Microbiology and Systems Biology TARA - Toxicology and Risk Assessment
ELSS - Earth, Life and Social Sciences
Biomedical Innovation
Biology
Healthy Living
Consumer exposure
Hair dyes
Margin of safety
Paraphenylenediamine
TK-based safety assessment
Toxicokinetics
Carbon phenylenediamine c 14
Hair dye
Phenylenediamine
Unclassified drug
Absorption
Adult
Blood analysis
Chemical reaction kinetics
Controlled study
Female
High performance liquid chromatography
Human
Human experiment
Male
Mass spectrometry
Metabolism
Population exposure
Radioactivity
Risk assessment
Skin test
Urinalysis
Urinary excretion
Rattus
To reference this document use:
http://resolver.tudelft.nl/uuid:123d6916-4ef5-4c0c-b1a7-01144bb87de4
DOI
https://doi.org/10.1016/j.fct.2015.04.003
TNO identifier
525598
ISSN
0278-6915
Source
Food and Chemical Toxicology, 81, 71-80
Document type
article