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EVALUATION OF EPIDERM FULL THICKNESS-300 (EFT-300) AS AN IN VITRO MODEL FOR SKIN IRRITATION: STUDIES ON ALIPHATIC HYDROCARBONS.

Mallampati1, R., Patlolla1, R.R., Agarwal1, S., Babu2, R.J., Hayden3, P., Klausner3, M., Singh1, M.S. 1College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA. 2Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. 3MatTek Corporation, 200 Homer Avenue, Ashland, MA 01721, USA.
Abstract

This study by scientists at Florida A&M University, Auburn University and MatTek Corp. demonstrated that MatTek’s EpiDermFT full-thickness in vitro 3-D human skin tissue equivalent is an excellent in vitro model for predicting in vivo irritation and understanding the structural activity relationship of saturated aliphatic hydrocarbons.The aim of this study was to understand the skin irritation effects of saturated aliphatic hydrocarbons (HCs), C9-C16, found in jet fuels using in vitro 3-dimensional EpiDerm full thickness-300 (EFT-300) skin cultures. The EFT-300 cultures were treated with 2.5 ul of HCs and the culture medium and skin samples were collected at 24 and 48 h to measure the release of various inflammatory biomarkers (IL-1a, IL-6 and IL-8). To validate the in vitro results, in vivo skin irritation studies were carried out in hairless rats by measuring trans epidermal water loss (TEWL) and erythema following un-occlusive dermal exposure of HCs for 72 h. The MTT tissue viability assay results with the EFT-300 tissue show that 2.5 ul/tissue (≅4.1 ul/cm2) of the HCs did not induce any significant changes in the tissue viability for exposure times up to 48 h of exposure. Microscopic observation of the EFT-300 cross-sections indicated that there were no obvious changes in the tissue morphology of the samples at 24 h, but after 48 h of exposure, tridecane, tetradecane and hexadecane produced a slight thickening and disruption of stratum corneum. Dermal exposures of C12-C16 HCs for 24 h significantly increased the expression of IL-1a in the skin as well as in the culture medium. Similarly, dermal exposure of all HCs for 24 h significantly increased the expression of interleukin-6 (IL-6) and IL-8 in the skin as well as in the culture medium in proportion to the HC chain length. As the exposure time increased to 48 h, IL-6 concentrations increased 2-fold compared to the IL-6 values at 24 h. The in vivo skin irritation data also showed that both TEWL and erythema scores increased with increased HCs chain length (C9-C16). In conclusion, the EFT-300 showed that the skin irritation profile of HCs was in the order of C9 < C10 < C11 < C12 < C13 ≅ C14 ≅ C16 and that the tissue was an excellent in vitro model to predict in vivo irritation and to understand the structural activity relationship of HCs.

Keywords

Aliphatic hydrocarbons, EpiDerm Full Thickness (EFT-300), Erythema, Hairless rats, IL-1a, IL-6, IL-8, In vivo skin irritation, Jet propellants (JPs), Kerosene based fuels, Skin irritation, TEWL, Tissue morphology

Materials Tested

Decane, Dodecane, Hexadecane, Nonane, Tetradecane, Tridecane

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