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.

ß-1,3-Glucan given orally modulates immunomyelopoietic activity and enhances the resistance of tumour-bearing mice.

ß-Glucans have been reported to be potent adjuvants in stimulating innate and adaptive immune responses. The aim of the present study was to determine the immunohematopoietic effects of Imunoglucan (HEBRON) following its oral administration to normal and Ehrlich ascites tumour (EAT)-bearing mice. Mice were treated with 250, 500 and 1000 mg/kg per day, p.o., Imunoglucan (ß-1,3-glucan extracted from Saccharomyces cerevisae) for 18 consecutive days. Treatment started 10 days prior to and ended 8 days after tumour inoculation. At 500 and 1000 mg/kg per day, Imunoglucan enhanced the life span of EAT-bearing mice and prevented myelosuppression and splenomegaly caused by the tumour by increasing the number of granulocyte-macrophage progenitors in the bone marrow and increasing colony-stimulating activity in the serum. At 500 mg/kg, Imunoglucan restored the reduced ability of stromal cells to display myeloid progenitors in long-term bone marrow cultures of EAT-bearing mice and upregulated the production of interleukin (IL)-6 and IL-1α by these cells, consistent with a higher number of non-adherent cells. Moreover, 500 mg/kg Imunoglucan restored natural killer cell activity in tumour-bearing mice, consistent with the increased production of interferon (IFN)-γ observed. The results of the present study suggest that Imunoglucan given orally indirectly modulates immune activity and probably disengages tumour-induced suppression by producing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (colony-stimulating factors, IL-1α, IL-6 and IFN-γ).