Assuring the safety of cosmetics and personal care products without testing in animals has long been the goal of many international companies. This concern has become even more important with the requirement of the Seventh Amendment to the Cosmetics Directive that after 2009 animal testing cannot be used to assess the eye or skin irritation potential of either cosmetics formulations or ingredients. To address this problem, the Alberto-Culver Company has developed a program to support the ocular safety evaluation of certain hair conditioners. This program relies on the results of a topical application of formulations to the surface of a three-dimensional, human cell-derived model of the corneal epithelium (EpiOcularTM, MatTek Corp., Ashland, MA, USA) and monitoring time to toxicity (ET50; MTT activity reduced to 50% of the control condition). Twenty-eight different formulations primarily based on either single or dual quaternary ammonium compound (quats) systems utilizing various combinations of seven different quats have been evaluated in the model. Potential safety of the materials was assessed by comparison to a benchmark material having a well established safety profile in commerce. Twenty-seven of the materials, including the benchmark, had ET50 values of 24 hours or greater, indicating that they were quite mild. The effectiveness of the system has been assessed by comparing the in vitro results with consumer experience information.