Abstracts / Toxicology Letters 172S (2007) S1–S240 S31 cutting/drying/styling. Ambient air and personal mon- itoring samples (vapours and particles), nasal and hand rinses were collected during all study phases. Urine (pre-exposure, quantitative samples for the 0–12, 12–24, 24–48 h periods after start of exposure) and blood samples (blank, 4, 8 or 24 h) were collected from all exposed subjects. Radioactivity was determined in all biological samples and study materials, tools and washing liquids, and a [ 14 C]-mass balance was per- formed daily. No adverse events were noted during the study. Waste, equipment, gloves and coveralls contained 0.41 ± 0.16%, dye mixing bowls 2.88 ± 0.54%, hair wash 45.47 ± 2.95%, hair + scalp 53.46 ± 4.06% of the applied radioactivity, respectively. Plasma levels were below the limit of quantification (≤10 ng PPD eq /mL). Total urinary 0–48 h excretion of [ 14 C] levels ranged from a total of <3–18 g PPD eq and was similar in subjects exposed during the different phases of hair dye- ing. Minimal air levels at or slightly above the limit of quantification were found in a few personal air mon- itoring samples during the phases of hair dyeing and hair cutting, but not during the rinsing phase. Air area monitoring samples or nasal rinses contained no mea- surable radioactivity. Hand residues ranged from 0.006 to 0.15 g PPD equivalents/cm 2 , and were found pre- dominantly after the cutting/drying phase. The mean mass balance of [ 14 C] across the 6 study days was 102.50 ± 2.20%. Overall, the mean, total systemic expo- sure of hairdressers to oxidative hair dyes during the hair dyeing process was estimated to be <0.33 g PPD eq /(kg body weight working day). Our results sug- gest that (a) current safety precautions for the handling of hair dyes offer sufficient protection against local and systemic exposure and (b) professional exposure to oxidative hair dyes does not pose a risk to human health. doi:10.1016/j.toxlet.2007.05.108 73 Metabolism of oxidative hair dyes: An overview of in vitro, in vivo, and clinical studies Julie Skare 1 , Gerhard Nohynek 2 , Robert Powrie 3 , Carsten Goebel 4 , Stefan Pfuhler 5 , Daniel Duche 2 , Andreas Zeller 5 , Marilyn Aardema 1 , Ting Hu 1 , Wim J.A. Meuling 6 1 The Procter & Gamble Company, Cincinnati, OH, United States; 2 L’Oreal Research & Development, Asnieres-sur-Seine, France; 3 CXR Biosciences Ltd., Dundee, United Kingdom; 4 Procter & Gamble-Wella Service GmbH, Darmstadt, Germany; 5 Procter & Gamble-Wella-cosmital SA, Marly, Switzerland; 6 TNO Quality of Life, 3700 AJ Zeist, The Netherlands Metabolism is important in the assessment of potential carcinogenicity of aromatic amines used in oxidative hair dyes because CYP-mediated N-hydroxylamine forma- tion is regarded as a key step in the activation of certain aromatic amines that are known human bladder carcino- gens (4-aminobiphenyl, 2-naphthylamine, benzidine). In addition, N-acetylation is a well-established pathway for metabolism of aromatic amines, and when cancer risk is modified by NAT2 genotype in epidemiology studies a causal role for an aromatic amine is inferred. Recent metabolism studies with the most widely used hair dye aromatic amines include in vitro studies of hepatic and skin metabolism, in vivo studies via the oral or dermal route, and a clinical study involving hair dye use. The results show that these compounds are N-acetylated in the skin by NAT1. This represents a detoxification pathway because, unlike the parent aro- matic amine, the N-acetylated metabolites tested in vitro are not genotoxic. Based on both in vitro and in vivo studies, N-acetylation is also a predominant hepatic metabolism pathway. There is no evidence for hep- atic metabolic activation (N-hydroxylation) typical of the carcinogenic aromatic amines. In vitro and in vivo studies indicate that hepatic phase II conjugation reac- tions (sulfation, glucuronidation) also represent major pathways for metabolism of some hair dyes, especially after oral administration. NAT2 genotype does not influ- ence the urinary metabolite profile of PPD in human subjects after hair dye use, which is inconsistent with the inference that hair dye use might be associated with an increased bladder cancer risk in NAT2 slow acetylators. doi:10.1016/j.toxlet.2007.05.109 74 N-Acetylation of aromatic amine hair dyes antagonizes haptenization Carsten Goebel 1 , Thomas Sieber 2 , Otto G¨ ottel 2 , Laurent Chassot 2 , Frank Gerberick 3 , Pierre Aeby 2 1 The Procter & Gamble Company, Wella Service GMBH, Darmstadt, Hessia, Germany; 2 The Procter & Gamble Company, Wella Cosmital, Marly, Fribourg, Switzerland; 3 The Procter & Gamble Company, Central Product Safety, Cincinnati, OH, United States A key element in the safety assessment of cosmetic chemicals is the prediction of their skin sensitizing properties. For aromatic amine hair dye precursors