Overview over ongoing ingredient issues Florian Schellauf, Colipa
Overview Colipa actively follows about 70 ingredient issues, 120 hair dye dossiers and monitors an additional 40 ingredient issues Therefore a selection: Parabens Nano TiO2 and ZnO Formaldehyde Expectations for 2009-2010
1. Parabens Colipa activity: Latest SCCP opinion confirms the validity of industry studies and requests additional confirmatory work The request is based on a proposal from industry which has been accepted by SCCP First, unaudited results of the study are available
Study design Groups of 12 male and 12 female rats received a single dermal, oral or subcutaneous (BuPB only) admin. of 100 mg/kg [ 14 C]-labelled Me-, Prop- or BuPB. [ 14 C]-label at phenyl moiety in order to clarify metabolism Blood samples at 0, 0.5, 1, 2, 4, 8, 12, 22 and 24 hrs for kinetics Urine and faeces up to 168 hours after dosing Sacrifice at 168 hrs, radioactivity in major organs and tissues Mass balance Plasma metabolites investigated by HPLC/UV/radioactivity monitoring in pooled blood samples at Cmax of kinetic groups Study compliant with G.L.P.
Conclusions - Kinetics Cmax and AUC: oral > subcut > dermal Principal excretion pathway: urine Kinetic-based systemic exposure Dermal route: Methyl > propyl > butyl Oral route: Methyl propyl butyl Subcut route (butyl only): similar to oral values, about 2-4fold dermal values Dermal absorption (basis of urinary excretion): 14/26%, 17/20% and 25/27% for methyl-, propyl- and butyl- in males and females, respectively Mass balance: acceptable (range: 91 to 115%)
Rat plasma spiked with Parabens and PHBA
No systemic exposure to parabens 8 hours after dermal application of Me-PB (100mg/kg) Plasma metabolite (PHBA) Premiminary results
No systemic exposure to parabens 8 hours after dermal application of Pr-PB (100mg/kg) Plasma metabolite (PHBA) Premiminary results
No systemic exposure to parabens 8 hours after dermal application of Bu-PB (100mg/kg) Plasma metabolite (PHBA) Premiminary results
No systemic exposure to parabens 8 hours after subcutaneous application of Bu-PB (100mg/kg) Plasma metabolite (PHBA) Premiminary results
Conclusions as of this moment In rats, parabens are well absorbed after oral administration, and partially absorbed after dermal or subcutaneous (BuPB only) administration Dermal absorption: MePB > ProPB BuPB Plasma concentrations consisted entirely of PHBA, independently of paraben chain length and route of administration Given that PHBA has no estrogenic activity and is ubiquitous in plants and human food, trace exposure of the human organism poses no health risk NB: aggregate human exposure to Bu-PB through cosmetics is as low as 0.016 mg/kg/day (MoS = >50000fold vs. Hoberman rat study) - Cowan-Ellsberry and Robison, Reg. Toxicol. Pharmacol., 2009
2. Nano TiO 2 and ZnO Colipa activity: Hearing with SCCS and SCENIHR Workplan for submission on TiO 2 and ZnO established Feb 09 Dossier on nano TiO 2 submitted - SCCS opinion awaited Submission on nano-zno by end of this year
Definitions and terminology Nanoparticle (1-100 nm) Particle with all three external dimensions at the nanoscale. [Alternative descriptions: Crystal Size, Primary Particle Size] Aggregate (30-150 nm) Particle comprising strongly bonded or fused particles where the resulting external surface area is significantly smaller than the sum of calculated surface areas of the individual components. [Alternative descriptions: Particle Size, Primary Particle Size] Agglomerate (1-100 µm) Collection of loosely bound particles or aggregates or mixtures of the two where the resulting external surface area is similar to the sum of surface areas of the individual components.
Definitions Nanoparticles Agglomerates Van der Waals forces X Shear forces Shear forces Aggregates Chemically bonded Smallest Structure possibly present Nanoparticles form aggregates and agglomerates in practical systems
Definitions: Particle size in the final formulation Powder Pre-dispersion Formulation 100nm TEM Agglomerate 1-100 microns Aggregate 30-150 nm
Particle size vs UV attenuation Extinction coefficient qe 70 60 50 40 30 20 10 0 290 340 390 440 490 540 Wavelength (nm) 220 nm 100 nm 50 nm 20 nm
W/O Sunscreen Formulation - TEM by BASF 100000 : 1 200nm
Absence of Dermal Penetration is a Key Factor Numerous studies confirm that nano-zno and nano-tio2 do not penetrate through skin. One example: Filipe et al. 2009 (EU sponsored NANODERM project):
3. Formaldehyde Re-classification of formaldehyde by IARC raises concerns and leads to discussions about re-classification of formaldehyde under the EU chemical legislation. Colipa survey amongst its membership: Usage of formaldehyde as such is limited to nail hardening products No use of formaldehyde as such as a preservative Preservatives releasing low levels of formaldehyde («formaldehyde releasers»)
Formaldehyde Commission recognises that possible concerns are not related to the preservative molecules themselves, but the low levels of formaldehyde released into the formulation. July 2008: Commission request for complete safety dossier on Formaldehyde Deadline for submission : Q1 2010 Colipa created a consortium on member companies, two suppliers and a few nail hardener manufacturers expressed interest. All necessary elements for the safety dossier are available Compilation of data into a SCCS dossier is well underway
Formaldehyde Colipa exposure study Approach: Mimicking the daily cosmetic routine of women to evaluate potential exposure to formaldehyde Aim: Establishing the potential inhalation exposure to formaldehyde emitted from finished products after topical application (up to 60 min) Personal air sampling (PAS) DNPH cartridges fitted to air-pumps ~1.5 l/min) Sampling lines connected close to the breathing zone
Formaldehyde Colipa exposure study 8 cosmetic finished products were tested (all commercial available products). 6 Subjects per product. Targeted amounts to be used/applied derived from the COLIPA database. Free formaldehyde content established in products according to 82/434/EEC Bathroom Measures: ~ 9.4 m3 Ventilation rate: 5/h (= 47 m3/h) Ambient temperature and R.H. registered during sampling via data logger.
Formaldehyde Colipa exposure study Restrictions: 1 day prior: No use of product (24 h) Only use of Sanex the morning on day 01 On day 01 Background bathroom (30 min) SAS Subject background (30 min) PAS Mean airborne (60 min) SAS T=0, application chair (60 min) n=6 samples T=0, use in shower shower (10 min) n=2; chair n=4 T=0, body lotion shower area (5 min) n=1; chair n=5
Formaldehyde Colipa exposure study Results: The formaldehyde levels measured: Aggregate maximum short-term exposure of 28 µg/m³ (~22 ppb). Individual maximum levels well below 10 µg/m³, often in the range of the background level. Maximum levels are reached mostly after 10 min, with a pronounced dicrease of concentration after An inhalation safety assessment demonstrates that these exposure levels do not pose a health risk The negligible risk is ~200 ppb (Connolly et al. 2004)
4. Expectations for 2009/2010 Season High profile ingredient submissions in 2009-2010: Nano-ZnO, Parabens (II), Formaldehyde, use of Iodine containing ingredients In 2008-2009 season: Discussions on Recast relatively little DG ENTR attention for ingredient issues Finalisation of the Recast increased focus on ingredient safety expected New Scientific Committee (SCCS) has started review work after a period of reorganisation
A glimpse into the future Ingredients expected to be in the EU Commission s spotlight: Hair dye substances Terpenes Additional nano-sized ingredients Traces of unwanted substances
Thank You! Florian Schellauf Issue Manager Science and Research COLIPA - The European Cosmetics Association Avenue Herrmann-Debroux 15A 1160 Brussels Tel. +32-2-227-6621 fschellauf@colipa.be