scholarly journals Ex Vivo Human Skin is not a Barrier for Cyclic Siloxanes (Cyclic Silicones): Evidence of Diffusion, Bioaccumulation, and Risk of Dermal Absorption Using a New Validated GC-FID Procedure

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 586 ◽  
Author(s):  
Dominika Krenczkowska ◽  
Krystyna Mojsiewicz-Pieńkowska ◽  
Bartosz Wielgomas ◽  
Dagmara Bazar ◽  
Zbigniew Jankowski

Cyclic methylsiloxanes D4, D5, D6 (also called cyclic silicones) are widely used in various dermatological products and cosmetics, both for children and adults. As a result of their unique physicochemical properties, the production of cyclic methylsiloxanes has greatly increased over the last few years, which has resulted in increased exposure to mankind. The validated quantitative for gas chromatography-flame ionization detector (GC-FID) analysis with using the transdermal diffusion system with vertical Franz cells demonstrated that ex vivo human skin is not a barrier to cyclic siloxanes. D4, D5, and D6 have a specific affinity to stratum corneum (SC) (especially D6), and can even diffuse into the deeper layers of the skin (epidermis (E) and dermis (D)), or into the receptor fluid as well. An important achievement of this work was the observation of the characteristic ratio partitioning D4, D5, and D6 in skin layers and receptor fluid (RF). The studies have shown that, in order to thoroughly understand the mechanism, it is important to determine not only the differences in the amounts of cumulated doses in total in all skin layers and receptor fluid, but also the mutual ratios of analyte concentrations existing between matrices. For example, in the case of the stratum corneum, the cumulative doses of D4, D5, and D6 were 27.5, 63.9, and 67.2 µg/cm2/24 h, respectively, and in the epidermis, they were 6.9, 29.9, and 10.7 µg/cm2/24 h, respectively, which confirmed the highest affinity of D6 to stratum corneum as the amount diffused into the epidermis was 2.8 times smaller compared to D5. The calculated epidermis-to-stratum corneum ratios of analyte concentrations also confirm this. The largest ratio was identified for D5 (E/SC = 47), followed by D4 (E/SC = 25), and finally by D6 (E/SC = 16). The analysis of the next stage of diffusion from epidermis to dermis revealed that in dermis the highest cumulative dose was observed for D5 (13.9 µg/cm2/24 h), while the doses of D4 and D6 were similar (5.1 and 5.3 µg/cm2/24 h). Considering the concentration gradient, it can be concluded that the diffusion of D5 and D6 occurs at a similar level, while D4 diffuses at a much higher level. These observations were also confirmed by the dermis-to-epidermis concentration ratios. The final stage of diffusion from dermis to the receptor fluid indicated that D4 was able to permeate easily, while D5 exhibited a difficult diffusion and the diffusion of D6 was limited. The receptor fluid-to-dermis concentration ratios (RF/D) were calculated for D4, D5, and D6: 80, 53, and 17, respectively. Our results also revealed the increased risk of D4 and D5 absorption into the blood and lymphatic systems, whereas D6 demonstrated the lowest risk. Therefore, we can argue that, among the three tested compounds, D6 is the safest one that can be used in dermatological, cosmetic, and personal care products. This study demonstrates that the stratum corneum, epidermis, and dermis can be also considered reservoirs of cyclic methylsiloxanes. Therefore, these compounds can demonstrate potential long-term bioaccumulation, and can be absorbed to the bloodstream in a long-term and uncontrolled process.

2017 ◽  
Vol 280 ◽  
pp. S107 ◽  
Author(s):  
Monica Andreassen ◽  
Martine M. Herud ◽  
Tone Rasmussen ◽  
Berit Granum ◽  
Ellen Namork ◽  
...  

2020 ◽  
Vol 68 ◽  
pp. 104954
Author(s):  
S. Kilo ◽  
J. Wick ◽  
S. Mini Vijayan ◽  
T. Göen ◽  
R.E. Horch ◽  
...  

2018 ◽  
Vol 1 (4) ◽  
pp. e201700009 ◽  
Author(s):  
Lizhe Zhuang ◽  
Kynan T Lawlor ◽  
Holger Schlueter ◽  
Zalitha Pieterse ◽  
Yu Yu ◽  
...  

The cellular and molecular microenvironment of epithelial stem/progenitor cells is critical for their long-term self-renewal. We demonstrate that mesenchymal stem cell–like dermal microvascular pericytes are a critical element of the skin's microenvironment influencing human skin regeneration using organotypic models. Specifically, pericytes were capable of promoting homeostatic skin tissue renewal by conferring more planar cell divisions generating two basal cells within the proliferative compartment of the human epidermis, while ensuring complete maturation of the tissue both spatially and temporally. Moreover, we provide evidence supporting the notion that BMP-2, a secreted protein preferentially expressed by pericytes in human skin, confers cell polarity and planar divisions on epidermal cells in organotypic cultures. Our data suggest that human skin regeneration is regulated by highly conserved mechanisms at play in other rapidly renewing tissues such as the bone marrow and in lower organisms such as Drosophila. Our work also provides the means to significantly improve ex vivo skin tissue regeneration for autologous transplantation.


2003 ◽  
Vol 11 (25) ◽  
pp. 3377 ◽  
Author(s):  
Yen Sun ◽  
Jiunn-Wen Su ◽  
Wen Lo ◽  
Sun-Jan Lin ◽  
Shiou-Hwa Jee ◽  
...  

1996 ◽  
Vol 24 (3) ◽  
pp. 311-315 ◽  
Author(s):  
E Pogliani ◽  
M Milani

Patients with chronic myeloproliferative disease are at increased risk of both thromboembolic and haemorrhagic complications. Cerebral thrombosis is a common cause of death in myeloproliferative disease patients. Picotamide is a new anti-platelet drug sharing a dual anti-thromboxane activity: inhibition of thromboxane A2 synthase and thromboxane A2 receptor antagonism. Picotamide inhibits in vitro and ex vivo platelet aggregation induced by different agonists. Interestingly, in vitro studies show that picotamide is able to increase prostacycline biosynthesis. In the clinical setting, picotamide treatment induces only a slight prolongation of bleeding time. The safety and efficacy of picotamide long-term treatment in 15 patients with essential thrombocytosis and a positive history of previous thromboembolic events was evaluated. After 12-month treatment with picotamide no patients suffered from thrombotic events and only one minor and transient bleeding episode was observed. This observational long-term trial shows that picotamide treatment in patients with thrombocytosis at high risk of thrombotic events is safe and well tolerated. Picotamide did not increase the risk of bleeding in these patients, while at the same time, no thrombotic events were observed during the 1-year treatment.


2016 ◽  
Vol 248 ◽  
pp. 25-33 ◽  
Author(s):  
Kathrin Dennerlein ◽  
Franklin Kiesewetter ◽  
Sonja Kilo ◽  
Thomas Jäger ◽  
Thomas Göen ◽  
...  

Cosmetics ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 50
Author(s):  
Manon Barthe ◽  
Clarisse Bavoux ◽  
Francis Finot ◽  
Isabelle Mouche ◽  
Corina Cuceu-Petrenci ◽  
...  

Cosmetic products need to have a proven efficacy combined with a comprehensive toxicological assessment. Before the current Cosmetic regulation N°1223/2009, the 7th Amendment to the European Cosmetics Directive has banned animal testing for cosmetic products and for cosmetic ingredients in 2004 and 2009, respectively. An increasing number of alternatives to animal testing has been developed and validated for safety and efficacy testing of cosmetic products and cosmetic ingredients. For example, 2D cell culture models derived from human skin can be used to evaluate anti-inflammatory properties, or to predict skin sensitization potential; 3D human skin equivalent models are used to evaluate skin irritation potential; and excised human skin is used as the gold standard for the evaluation of dermal absorption. The aim of this manuscript is to give an overview of the main in vitro and ex vivo alternative models used in the safety testing of cosmetic products with a focus on regulatory requirements, genotoxicity potential, skin sensitization potential, skin and eye irritation, endocrine properties, and dermal absorption. Advantages and limitations of each model in safety testing of cosmetic products are discussed and novel technologies capable of addressing these limitations are presented.


2004 ◽  
Vol 97 (6) ◽  
pp. 1149-1160 ◽  
Author(s):  
S. Messager ◽  
A.C. Hann ◽  
P.A. Goddard ◽  
P.W. Dettmar ◽  
J.-Y. Maillard

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