In quantitative risk assessment, the Threshold of Toxicological Concern (TTC) approach provides a method to determine a conservative estimate of a chronic exposure below which there is a very low probability of risk.The TTC concept is a principle, which through a probabilistic approach, establishes human exposure levels for chemicals below which there would be no appreciable risk to human health.TTC is reliant on existing oral toxicity data on a multitude of chemical classes to predict the toxicological potential of non-tested chemicals.The tiered TTC approach has 6 potency tiers covering 4 orders of magnitude (Kroes et al.2004).The upper tiers are based on non-cancer data from a reference database of over 600 chemicals analyzed by Munro et al (1996) and grouped according to the Cramer et al (1978) decision tree according to chemical structure.The utility of TTC has been well established and accepted by regulatory bodies in a number of areas e.g.food packaging migrants, flavor chemicals, genotoxic impurities in pharmaceuticals.In fact, low level constituents or contaminants in a cosmetic product often have insufficient toxicological data to make a full assessment of chronic toxicity.As one of the practical alternatives to repeated dose toxicity testing, the TTC approach is now being expanded to include cosmetics-related chemicals.TTC supports exposure-based safety assessment with a threshold for chemicals below which there is a low probability of a risk to humans.The EU Cosmetics Regulation requires replacement of animal testing of cosmetic products for repeated dose/reproductive toxicity and toxicokinetics.To this end, the COSMOS consortium within SEURAT, a joint cluster between European Commission and Cosmetics Europe, has been engaged in development of computational methods and tools.COSMOS has developed a new toxicity database enriched with oral repeated dose studies for cosmetics-related chemicals.A new Cosmetics Inventory has been defined based on the chemical records from EU COSING database and list from the US Personal Care Products Council.The sources for toxicity data include US Food and Drug Administration, US Environmental Protection Agency, EU Scientific Committee of Consumer Safety, European Chemical Agency, US National Toxicology Program, and literature publications.A new non-cancer TTC database for cosmetics-related chemicals has been compiled by augmenting the COSMOS database with substances from the Munro dataset found in the Cosmetics Inventory.The resulting TTC database contains over 500 chemical structures with oral no-observed-adverse-effect-levels (NOAEL); the toxicity data for the lowest 10th percentile have been further scrutinized in quality control sessions.The inclusion and selection criteria of the NOAEL decisions have been documented transparently.The chemical space of the new TTC database has been compared with other existing TTC databases to demonstrate the coverage suitable for the assessment of cosmetics products.