This directive will be replaced stepwise by the new EC Cosmetics regulation 1223/2009 (so called Recast, European Parliament and Council, 2009). Under both regulations, the toxicological profile of all used ingredients and detailed knowledge of the product-specific exposure are required as fundamental for the safety assessment. State-of-the-art concepts for the safety assessment of products with intentional exposure of skin, mucous membranes or the oral cavity have been described elsewhere (Mildau et al., 2007, Rossow et al., 2005, SCCS, 2010 and Mildau and Huber,

2010). Therefore, this review will focus Protein Tyrosine Kinase inhibitor on inhalation risk assessment only. Recently discussed new concepts in regulatory toxicology, such as the threshold of toxicological concern (TTC) or the “point of departure”

replacing the no-observable-effect-level are outside of the scope of this article, but could eventually extend to safety assessment of sprays in the future. Based on the variability of how consumer use cosmetic spray products, Veliparib regulatory and scientific experts have developed a number of models for quantitative exposure assessment. Several of these models are often based on unpublished data and are not formally harmonised within the cosmetics industry. In 2010 the SCCS published a first opinion taking into account inhalation exposure evaluating the risk of dihydroxyacetone for self tanning products applied in spray cabines (SCCS/1347/10, 2010). In broad ranges the SCCS Opinion is in line with the approach described in this manuscript and as is currently used from major parts of the cosmetic industry. The intention of this paper is to propose some basic methodological approaches and procedures in order to facilitate a harmonised and transparent safety assessment of cosmetic

sprays. This paper is not intended to be a binding industry standard but a recommendation to use these tools in the sense of a Weight-of-Evidence Approach (WoE) when conducting the safety assessment. In order to assess the Etofibrate safety of cosmetic spray products, this paper outlines the major steps that need to be followed including (1) understanding exposure either by modelling or by measurement, (2) understanding systemic and local exposure of the respiratory tract and (3) using data on local toxicity and systemic toxicity to establish margins of safety (MoS) and/or margins of exposure (MoE) needed for the final risk assessment. Cosmetic products used for spray applications are generally composed of the cosmetic product formulation, often containing the active ingredient(s), and an appropriate solvent. Such composition is filled in pressure resistant containers equipped with product specific spray nozzles. For propellant driven spray applications, pressurised propellant mix is finally added.