Preliminary safety assessment of C-8 xylitol monoester and xylitol phosphate esters.

OBJECTIVES: 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. CONCLUSION: Our results suggested that xylitol-derived compounds appear to be suitable candidates for preservative systems in cosmetics.

In vitro evaluation of the efficacy of commercial green tea extracts in UV protection.

Plants with antioxidant properties are beneficial for preventing the ageing events evoked by UV light, and numerous products based on Camellila sinensis (green tea) are commercially available, many of which claiming to contain bioactive compounds that would prevent UV-induced skin damage. In this study, we tested the efficacy of five commercial green tea extracts used to enrich cosmetic formulations for protecting human and mouse fibroblasts against UV radiation effects and compared with a fluid one prepared according to the Brazilian Pharmacopoeia recommendations. Taking into consideration that the ageing process can be accelerated by solar radiation by excessive free radical generation, leading to depletion of skin antioxidant defences, and its collapse caused by disruption of the metalloproteinase metabolism, we have used their individual (-)-epigallocathechin-3-gallate (EGCG) content, the catalase and SOD status and the matrix-degrading metalloproteases (MMP)-1, MMP-9 and MMP-13 levels as comparative parameters. The EGCG content of the commercial products showed wide variability, ranging from undetectable levels to 58.65 ± 1.12 µg mL(-1) , in contrast with the fluid extract (87.82 ± 1.35 µg mL(-1) ). Moreover, only the pharmacopoeic extract was able to significantly reduce MMP degradation while enhancing the levels of SOD and catalase. These results indicate, for the first time, that the methodologies for preparing herbal mixtures can interfere significantly with compounds endowed with photoprotective effects, and the efficacy of products containing C. sinensis extracts thought to act against effects of solar radiation can be compromised.

Ehrlich ascites tumor as a tool in the development of compounds with immunomodulatory properties.

In previous works, we have demonstrated that the myeloprotective properties of several natural and synthetic compounds are partly responsible for their antitumor activity in the Ehrlich ascites tumor (EAT) model. In this work, we present information that may be useful to the study of pharmacological and toxicological properties of compounds that affect the hematological compartment. Clonogenic studies in EAT-inoculated mice demonstrated a rapid decrease in bone marrow CFU-GM, whereas a progressive increase in splenic CFU-GM and cellularity was observed, followed by splenomegaly. Bone marrow cellularity declined on the third day after tumor challenge, returning to normal values thereafter. Serum from EAT-bearing mice produced detectable colony-stimulating activity in vitro. Similar results were observed with the conditioned medium from Ehrlich tumor cell cultures, but not with the cell-free Ehrlich tumor ascitic fluid. Tumor inoculation also resulted in a more striking depletion in the number of non-adherent cells in long-term bone marrow cell cultures (LTBMCs) with no bone marrow stroma formation. We speculate that the physiological alterations induced by the EAT growth can be used to assess the ability of compounds to modulate the hematopoietic response.