The Carba Mix-In Vitro Investigations of Potential Cocktail Effects in Patch Tests With Rubber Allergens.

BACKGROUND: The carba mix is used to screen rubber chemical allergy and consists of three rubber sensitising chemicals: 1% (w/w) zinc diethyldithiocarbamate (ZDEC), 1% (w/w) zinc dibutyldithiocarbamate (ZDBC) and 1% (w/w) 1,3-diphenylguanidine (DPG), all in petrolatum. However, carba mix patch test results can be difficult to interpret, which may be linked to so-called 'cocktail' effects. OBJECTIVES: The carba mix was used as a 'model mixture' to better understand human reactions observed in clinical patch testing. METHODS: We investigated the responses of a human cell model resembling dendritic cells to the carba mix single constituents ZDEC, ZDBC and DPG and to predefined mixtures capturing the molar composition of the carba mix using transcriptomic approaches and immunological and biochemical assays. RESULTS: We detected unique cell responses to individual chemicals, where DPG was inducing ROS production and affecting autophagic flux. The combination of ZDEC, ZDBC and DPG induced higher levels of IL-8 secretion than expected based on the IL-8 levels in response to single chemical exposures. CONCLUSIONS: The data collected in this study support the hypothesis that the carba mix can give rise to cocktail effects. Considering exposure profiles, patch testing with separate carba mix sensitisers may be more appropriate.