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Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients

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Author: Kroes, R. · Renwick, A.G. · Feron, V. · Galli, C.L. · Gibney, M. · Greim, H. · Guy, R.H. · Lhuguenot, J.C. · Sandt, J.J.M. van de
Institution: TNO Kwaliteit van Leven
Source:Food and Chemical Toxicology, 12, 45, 2533-2562
Identifier: 240460
doi: doi:10.1016/j.fct.2007.06.021
Keywords: Chemistry Safety · Analytical research · Cosmetic ingredients · Risk assessment · Threshold of toxicological concern (TTC) · Trans-dermal absorption · cosmetic · flavoring agent · article · chemical structure · comparative study · drug exposure · first pass effect · food · human · nonhuman · physical chemistry · risk assessment · Administration, Cutaneous · Administration, Oral · Cosmetics · Decision Support Techniques · Decision Trees · Humans · No-Observed-Adverse-Effect Level · Safety · Toxicity Tests


The threshold of toxicological concern (TTC) has been used for the safety assessment of packaging migrants and flavouring agents that occur in food. The approach compares the estimated oral intake with a TTC value derived from chronic oral toxicity data for structurally-related compounds. Application of the TTC approach to cosmetic ingredients and impurities requires consideration of whether route-dependent differences in first-pass metabolism could affect the applicability of TTC values derived from oral data to the topical route. The physicochemical characteristics of the chemical and the pattern of cosmetic use would affect the long-term average internal dose that is compared with the relevant TTC value. Analysis has shown that the oral TTC values are valid for topical exposures and that the relationship between the external topical dose and the internal dose can be taken into account by conservative default adjustment factors. The TTC approach relates to systemic effects, and use of the proposed procedure would not provide an assessment of any local effects at the site of application. Overall the TTC approach provides a useful additional tool for the safety evaluation of cosmetic ingredients and impurities of known chemical structure in the absence of chemical-specific toxicology data. © 2007 Elsevier Ltd. All rights reserved.