INCORPORATION OF RECONSTRUCTED HUMAN EPIDERMAL TISSUES INTO A CORPORATE TOXICOLOGY LABORATORY: USE OF IN VITRO TEST DATA FOR DIVERSE SAFETY AND RISK ASSESSMENT APPLICATIONS.

The 3M Strategic Toxicology Laboratory (STL) is an internal corporate resource providing toxicology support to 3M businesses. An objective in the STL is to routinely incorporate in vitro test methods, with a recent focus on the use of reconstructed human epidermis (RhE) tissues.. The first model utilized has been EpiDerm™, which is currently validated for classification of chemicals for dermal irritation in OECD 439, and also dermal corrosion in OECD 431. Following the process outlined in the standard protocols for demonstration of technical proficiency, both test methods have been validated and used to assist with classification of chemistries for consumer and industrial use, utilizing the standardized MTT based cell viability assay. In addition, custom protocols have been performed using the tissues in time course irritation studies to evaluate the release of the inflammatory marker cytokine IL-1α. This approach has been advantageous for the simultaneous screening of multiple formulations for irritation potential during research and development for new products. Other customized studies have evaluated the efficacy of various skin washing agents at removal of a viscous coating from the skin tissues, in a simulated washing study to help formulate occupational health recommendations for workers. These studies evaluated irritation potential using MTT, IL-1α and LDH release, and also analyzed the dermal penetration of an amine component in the coating. In summary, incorporation of these test methods has been very useful for the evaluation of a multitude of dermal exposure scenarios. The tissues have been used in standardized irritation and corrosion assays, as well as custom protocols utilizing additional markers of cell damage, and also specialized skin washing and dermal penetration studies. The results of these studies have provided valuable information for safety and risk assessment purposes, particularly during the product development phases, and have permitted these evaluations without animal use.

Corrosion GHS classification, IL-1a, LDH, OECD 431, OECD 439, Skin corrosion test, Skin irritation test, Viscous coating, Washing agents

1,2‐Diaminopropane Octanoic (Caprylic) acid, 1‐bromohexane, 1-methyl‐3‐phenyl‐1‐piperazine, 2‐tert‐Butylphenol, 4‐Amino‐1,2,4‐triazole, Boron trifluoride dihydrate, cyclamen aldehyde, Dove wash, heptanal, heptyl butyrate, hexyl salicylate, isopropanol, Isostearic acid (2‐heptyl‐decanoic acid), Methacrolein, Methyl palmitate, methyl stearate, N,N’‐Dimethyl dipropylenetriamine, naphthalene acetic acid, Neutrogena wash, Phenethyl bromide, potassium hydroxide (5% aq), potassiumhydroxide, Sodium bisulfite, Softicide wash, Tetrachloroethylene