Described herein is an in vitro alternative method to replace or augment the Draize rabbit skin irritation test for human skin irritation prediction. This in vitro model consists of a three-dimensional human skin co-culture (HuK/F) of keratinocytes and fibroblasts seeded onto medical grade nylon mesh. A battery of assays predictive of skin irritation using cytotoxicity and pro-inflammatory endpoints are used. These assays are used to evaluate compositions which come into contact with the skin, particularly anionic, cationic and nonionic surfactants, across an array of irritancy potential. For prostaglandin generation and cell viability endpoints, the in vitro co-culture system endpoints correlated well with human skin patch irritation data.