title: Preliminary safety assessment of C-8 xylitol monoester and xylitol phosphate esters.
abstract: OBJECTIVE
  Most of the cosmetic compounds with preservative properties available in the market pose some risks concerning safety, such as the possibility of causing sensitization. Due to the fact that there are few options, the proper development of new molecules with this purpose is needed. Xylitol is a natural sugar, and the antimicrobial properties of xylitol-derived compounds have already been described in the literature. C-8 xylitol monoester and xylitol phosphate esters may be useful for the development of skincare products. As an initial screen for safety of chemicals, the combination of in silico methods and in vitro testing can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal and human testing. This study was designed to evaluate the safety of C-8 xylitol monoester and xylitol phosphate esters regarding carcinogenicity, mutagenicity, skin and eye irritation/corrosion and sensitization through alternative methods.
  
  
  METHODS
  For the initial safety assessment, quantitative structure-activity relationship methodology was used. The prediction of the parameters carcinogenicity/mutagenicity, skin and eye irritation/corrosion and sensitization was generated from the chemical structure. The analysis also comprised physical-chemical properties, Cramer rules, threshold of toxicological concern and Michael reaction. In silico results of candidate molecules were compared to 19 compounds with preservative properties that are available in the market. Additionally, in vitro tests (Ames test for mutagenicity, cytotoxicity and phototoxicity tests and hen's egg test--chorioallantoic membrane for irritation) were performed to complement the evaluation.
  
  
  RESULTS
  In silico evaluation of both molecules presented no structural alerts related to eye and skin irritation, corrosion and sensitization, but some alerts for micronucleus and carcinogenicity were detected. However, by comparison, C-8 xylitol monoester, xylitol phosphate esters showed similar or better results than the compounds available in the market. Concerning experimental data, phototoxicity and mutagenicity results were negative. As expected for compounds with preservative activity, xylitol-derived substances presented positive result in cytotoxicity test. In hen's egg test, both molecules were irritants.
  
  
  CONCLUSIONS
  Our results suggested that xylitol-derived compounds appear to be suitable candidates for preservative systems in cosmetics.
authors.affiliation: Department of Pharmacology/Hemocenter, Faculty of Medical Science, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: J E P S
authors.initials: JE
authors.lastname: Silveira
authors.affiliation: Research and Development Department, Chemyunion Química Ltda, Sorocaba, SP, Brazil.
authors.forename: M C V
authors.initials: MC
authors.lastname: Pereda
authors.affiliation: Research and Development Department, Chemyunion Química Ltda, Sorocaba, SP, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Nogueira
authors.affiliation: Department of Pharmacology/Hemocenter, Faculty of Medical Science, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Dieamant
authors.affiliation: Research and Development Department, Chemyunion Química Ltda, Sorocaba, SP, Brazil.
authors.forename: C K M
authors.initials: CK
authors.lastname: Cesar
authors.forename: K M
authors.initials: KM
authors.lastname: Assanome
authors.affiliation: Department of Pharmacology/Hemocenter, Faculty of Medical Science, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Silva
authors.affiliation: Department of Pharmacology/Hemocenter, Faculty of Medical Science, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: C O
authors.initials: CO
authors.lastname: Torello
authors.affiliation: Department of Pharmacology/Hemocenter, Faculty of Medical Science, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: M L S
authors.initials: ML
authors.lastname: Queiroz
authors.affiliation: Department of Pharmacology/Hemocenter, Faculty of Medical Science, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Eberlin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D003358:Cosmetics / Q000009:adverse effects*; D004952:Esters / Q000737:chemistry; D006801:Humans; D051379:Mice; D011310:Preservatives, Pharmaceutical; D014993:Xylitol / Q000737:chemistry*
chemical_list: D003358:Cosmetics; D004952:Esters; D011310:Preservatives, Pharmaceutical; D014993:Xylitol
keywords: chemical analysis; computer modeling; preservatives; safety testing; xylitol