Integrated risk assessment of a hydroxyapatite-protein-composite for use in oral care products: a weight-of-evidence case study.
Risk assessment of cosmetic ingredients represents a regulatory standard requirement in Europe and other regions. An integrated approach was designed to assess the safety of HPC, a particulate composite of hydroxyapatite and protein (gelatin) for use in oral care products, employing a weight-of-evidence assessment and considering specific physico-chemical properties and exposure conditions. An initial evaluation of the constituents suggested that their chemical nature does not represent a particular health hazard per se. Hydroxyapatite is the main component of teeth and bones in mammals; gelatin is used in food and assumed to be safe once a BSE/TSE risk has been excluded. In vitro screening tests were chosen to further evaluate the biocompatibility: Hen's egg test-chorioallantoic membrane (HET-CAM) to assess irritating effects towards mucous membranes; MTT cytotoxicity test with 3T3 fibroblasts; human corneal epithelial models to investigate inflammatory mediators and cytotoxicity; macrophage assays to measure cytotoxicity, inflammatory mediators and oxidative stress. Together with results from clinical studies, exposure estimates and analyses of kinetic properties, the presented information provides sound evidence to support the safe use of HPC. This is an example of a risk assessment for cosmetic use of small particles without the need for additional animal studies.
Henkel AG & Co. KGaA, Corporate Product Safety, Department of Human Safety Assessment, Düsseldorf, Germany. julia.scheel@henkel.com
Julia
J
Scheel
Martina
M
Hermann
D000180:Acrylic Resins / Q000008:administration & dosage / Q000009:adverse effects / Q000633:toxicity*; D000818:Animals; D041702:BALB 3T3 Cells; D002642:Chick Embryo; D003188:Composite Resins / Q000008:administration & dosage / Q000009:adverse effects / Q000633:toxicity*; D003257:Consumer Product Safety; D003358:Cosmetics / Q000008:administration & dosage / Q000009:adverse effects / Q000633:toxicity; D017886:Durapatite / Q000008:administration & dosage / Q000009:adverse effects / Q000633:toxicity*; D005780:Gelatin / Q000008:administration & dosage / Q000009:adverse effects / Q000633:toxicity*; D006801:Humans; D051379:Mice; D011140:Polyurethanes / Q000008:administration & dosage / Q000009:adverse effects / Q000633:toxicity*; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D018570:Risk Assessment; D014100:Toothpastes / Q000009:adverse effects
D000180:Acrylic Resins; C029012:Composite Dental Resin; D003188:Composite Resins; D003358:Cosmetics; D011140:Polyurethanes; D014100:Toothpastes; C031361:Cosmic composite resin; D005780:Gelatin; D017886:Durapatite