Draize human repeat insult patch test (HRIPT): Seven decades of pitfalls and progress

Allergic contact dermatitis, a Type IV delayed hypersensitivity reaction, can result in dermatologic signs/symptoms for patients/workers. The likelihood of this phenomenon has been estimated/predicted for numerous chemicals/drugs by animal model and human patch testing protocols developed over the last century. Karl Landsteiner initiated testing with guinea pig studies; further studies based on his initial concept were in continual development. John Draize extended Landsteiner's guinea pig studies (which led to development of blood transfusions) to a human assay documenting irritant and allergic contact dermatitis potential - for drugs, chemicals, mixtures and products. We performed a literature search of major Draize derived protocols of the human repeat insult patch test (HRIPT). Our results reveal minor and major differences between protocols and lack of international standardization. Key clarification and principles post-Draize modified and improved usefulness of the HRIPT. Without a standard method of performing the HRIPT, it is problematic to generalize results of studies summarized here. Furthermore, we suggest a potential standardization procedure/protocol combining the work of the most satisfactory HRIPT methods. As the HRIPT constitutes a key parameter in current quantitative risk assessment for chemicals/drugs, such standardization should aid potential prediction of allergic contact dermatitis potential.